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Special Issue "Oxidative Stress in Cardiovascular Disease 2015"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 June 2015)

Special Issue Editors

Guest Editor
Prof. Dr. Francis J. Miller Jr.

Departments of Internal Medicine and Anatomy and Cell Biology, University of Iowa, Veterans Affairs Medical Center, Iowa City, Iowa, USA
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Interests: atherosclerosis; reactive oxygen species; oxidative stress; smooth muscle cells; NADPH oxidases; restenosis; redox signaling
Guest Editor
Dr. Gabor Csanyi

Department of Pharmacology and Toxicology, Vascular Biology Center, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA
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Interests: oxidative stress, reactive oxygen species, NADPH oxidase, cardiovascular disease, vascular tone dysfunction, thrombospondins, nitric oxide, prostanoids, and EDHF
Guest Editor
Dr. Grant Drummond

Department of Pharmacology, Monash University, Victoria 3800, Australia
Website | E-Mail

Special Issue Information

Dear Colleagues,

Cardiovascular disease is the leading cause of mortality and the most expensive health condition in the United States. Animal and human data implicate increased levels of reactive oxygen species (ROS) associated with oxidative stress in the pathogenesis of cardiovascular disease. Whereas ROS are essential for normal cellular processes, the molecular effects of increased ROS include the oxidation of DNA, RNA, lipids and proteins resulting in the dysregulation of ion channels, signaling pathways and transcription factors. However, we still do not have a complete understanding of the underlying mechanisms and consequences of increased ROS generation in cardiovascular tissue. Reducing oxidative stress represents a promising approach for prevention and treatment of cardiovascular disease. However, in numerous clinical trials, antioxidant supplementation failed to reduce cardiovascular morbidity or mortality. Therefore, alternative strategies are to achieve targeted delivery of antioxidants or to inhibit specific enzymatic sources of ROS, which include the mitochondria, NADPH oxidases, xanthine oxidase, lipooxygenase, cyclooxygenase, and nitric oxide synthase. This special issue will focus on the causes and consequence of oxidative stress in cardiovascular disease and explore emerging treatment strategies.

Prof. Dr. Francis Miller, Jr.
Dr. Gabor Csanyi
Dr. Grant Drummond
Guest Editors

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Keywords

  • oxidative stress, reactive oxygen species
  • heart disease, myocardial infarction, ischemia/reperfusion, preconditioning
  • vascular disease, atherosclerosis, hypertension, restenosis, stroke, thrombosis
  • biomarkers of oxidative stress
  • redox-mediated signaling
  • transcription factors, antioxidant response elements
  • antioxidant therapy

Related Special Issue

Published Papers (23 papers)

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Research

Jump to: Review

Open AccessArticle Relationship between Proinflammatory and Antioxidant Proteins with the Severity of Cardiovascular Disease in Type 2 Diabetes Mellitus
Int. J. Mol. Sci. 2015, 16(5), 9469-9483; doi:10.3390/ijms16059469
Received: 26 February 2015 / Revised: 1 April 2015 / Accepted: 8 April 2015 / Published: 27 April 2015
Cited by 9 | PDF Full-text (1103 KB) | HTML Full-text | XML Full-text
Abstract
Type 2 diabetes mellitus patients are at significant risk of cardiovascular disease, however, the pathophysiology of these complications is complex and incompletely known in this population. The aim of this study was to compare the serum proteome of patients with type 2 diabetes
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Type 2 diabetes mellitus patients are at significant risk of cardiovascular disease, however, the pathophysiology of these complications is complex and incompletely known in this population. The aim of this study was to compare the serum proteome of patients with type 2 diabetes mellitus presenting or not presenting cardiovascular disease with non-diabetic subjects to find essential proteins related to these cardiovascular complications. This cross-sectional study compares the serum proteome by a combination of protein depletion with 2D-DIGE (2-dimension Difference Gel Electrophoresis) methodology. The proteins differentially expressed were identified by MALDI TOF/TOF (Matrix-assisted laser desorption/ionization and Time-Of-Flight ion detector) or LC-MS/MS (Liquid Chromatography coupled to Mass-Mass Spectrometry). Type 2 diabetes mellitus patients with cardiovascular disease showed higher expression of plasma retinol binding protein and glutathione peroxidase-3 compared to those without cardiovascular disease and non-diabetic controls. These results show that proteins related to the inflammatory and redox state appear to play an important role in the pathogenesis of the cardiovascular disease in the type 2 diabetes mellitus patients. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
Open AccessArticle Preservation of Renal Blood Flow by the Antioxidant EUK-134 in LPS-Treated Pigs
Int. J. Mol. Sci. 2015, 16(4), 6801-6817; doi:10.3390/ijms16046801
Received: 4 November 2014 / Accepted: 6 March 2015 / Published: 25 March 2015
PDF Full-text (854 KB) | HTML Full-text | XML Full-text
Abstract
Sepsis is associated with an increase in reactive oxygen species (ROS), however, the precise role of ROS in the septic process remains unknown. We hypothesized that treatment with EUK-134 (manganese-3-methoxy N,N'-bis(salicyclidene)ethylene-diamine chloride), a compound with superoxide dismutase and catalase activity,
[...] Read more.
Sepsis is associated with an increase in reactive oxygen species (ROS), however, the precise role of ROS in the septic process remains unknown. We hypothesized that treatment with EUK-134 (manganese-3-methoxy N,N'-bis(salicyclidene)ethylene-diamine chloride), a compound with superoxide dismutase and catalase activity, attenuates the vascular manifestations of sepsis in vivo. Pigs were instrumented to measure cardiac output and blood flow in renal, superior mesenteric and femoral arteries, and portal vein. Animals were treated with saline (control), lipopolysaccharide (LPS; 10 µg·kg−1·h−1), EUK-134, or EUK-134 plus LPS. Results show that an LPS-induced increase in pulmonary artery pressure (PAP) as well as a trend towards lower blood pressure (BP) were both attenuated by EUK-134. Renal blood flow decreased with LPS whereas superior mesenteric, portal and femoral flows did not change. Importantly, EUK-134 decreased the LPS-induced fall in renal blood flow and this was associated with a corresponding decrease in LPS-induced protein nitrotyrosinylation in the kidney. PO2, pH, base excess and systemic vascular resistance fell with LPS and were unaltered by EUK-134. EUK-134 also had no effect on LPS-associated increase in CO. Interestingly, EUK-134 alone resulted in higher CO, BP, PAP, mean circulatory filling pressure, and portal flow than controls. Taken together, these data support a protective role for EUK-134 in the renal circulation in sepsis. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
Open AccessArticle SOD2 Activity Is not Impacted by Hyperoxia in Murine Neonatal Pulmonary Artery Smooth Muscle Cells and Mice
Int. J. Mol. Sci. 2015, 16(3), 6373-6390; doi:10.3390/ijms16036373
Received: 30 January 2015 / Revised: 9 March 2015 / Accepted: 12 March 2015 / Published: 19 March 2015
Cited by 4 | PDF Full-text (964 KB) | HTML Full-text | XML Full-text
Abstract
Pulmonary hypertension (PH) complicates bronchopulmonary dysplasia (BPD) in 25% of infants. Superoxide dismutase 2 (SOD2) is an endogenous mitochondrial antioxidant, and overexpression protects against acute lung injury in adult mice. Little is known about SOD2 in neonatal lung disease and PH. C57Bl/6 mice
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Pulmonary hypertension (PH) complicates bronchopulmonary dysplasia (BPD) in 25% of infants. Superoxide dismutase 2 (SOD2) is an endogenous mitochondrial antioxidant, and overexpression protects against acute lung injury in adult mice. Little is known about SOD2 in neonatal lung disease and PH. C57Bl/6 mice and isogenic SOD2+/+ and SOD2−/+ mice were placed in room air (control) or 75% O2 (chronic hyperoxia, CH) for 14 days. Right ventricular hypertrophy (RVH) was assessed by Fulton’s index. Medial wall thickness (MWT) and alveolar area were assessed on formalin fixed lung sections. Pulmonary artery smooth muscle cells (PASMC) were placed in 21% or 95% O2 for 24 h. Lung and PASMC protein were analyzed for SOD2 expression and activity. Oxidative stress was measured with a mitochondrially-targeted sensor, mitoRoGFP. CH lungs have increased SOD2 expression, but unchanged activity. SOD2−/+ PASMC have decreased expression and activity at baseline, but increased SOD2 expression in hyperoxia. Hyperoxia increased mitochondrial ROS in SOD2+/+ and SOD2−/+ PASMC. SOD2+/+ and SOD2−/+ CH pups induced SOD2 expression, but not activity, and developed equivalent increases in RVH, MWT, and alveolar area. Since SOD2−/+ mice develop equivalent disease, this suggests other antioxidant systems may compensate for partial SOD2 expression and activity in the neonatal period during hyperoxia-induced oxidative stress. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
Open AccessArticle l-Cystathionine Inhibits the Mitochondria-Mediated Macrophage Apoptosis Induced by Oxidized Low Density Lipoprotein
Int. J. Mol. Sci. 2014, 15(12), 23059-23073; doi:10.3390/ijms151223059
Received: 27 October 2014 / Revised: 28 November 2014 / Accepted: 4 December 2014 / Published: 11 December 2014
Cited by 4 | PDF Full-text (3164 KB) | HTML Full-text | XML Full-text
Abstract
This study was designed to investigate the regulatory role of l-cystathionine in human macrophage apoptosis induced by oxidized low density lipoprotein (ox-LDL) and its possible mechanisms. THP-1 cells were induced with phorbol 12-myristate 13-acetate (PMA) and differentiated into macrophages. Macrophages were incubated with
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This study was designed to investigate the regulatory role of l-cystathionine in human macrophage apoptosis induced by oxidized low density lipoprotein (ox-LDL) and its possible mechanisms. THP-1 cells were induced with phorbol 12-myristate 13-acetate (PMA) and differentiated into macrophages. Macrophages were incubated with ox-LDL after pretreatment with l-cystathionine. Superoxide anion, apoptosis, mitochondrial membrane potential, and mitochondrial permeability transition pore (MPTP) opening were examined. Caspase-9 activities and expression of cleaved caspase-3 were measured. The results showed that compared with control group, ox-LDL treatment significantly promoted superoxide anion generation, release of cytochrome c (cytc) from mitochondrion into cytoplasm, caspase-9 activities, cleavage of caspase-3, and cell apoptosis, in addition to reduced mitochondrial membrane potential as well as increased MPTP opening. However, 0.3 and 1.0 mmol/L l-cystathionine significantly reduced superoxide anion generation, increased mitochondrial membrane potential, and markedly decreased MPTP opening in ox-LDL + l-cystathionine macrophages. Moreover, compared to ox-LDL treated-cells, release of cytc from mitochondrion into cytoplasm, caspase-9 activities, cleavage of caspase-3, and apoptosis levels in l-cystathionine pretreated cells were profoundly attenuated. Taken together, our results suggested that l-cystathionine could antagonize mitochondria-mediated human macrophage apoptosis induced by ox-LDL via inhibition of cytc release and caspase activation. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
Open AccessArticle Over-Expression of Copper/Zinc Superoxide Dismutase in the Median Preoptic Nucleus Attenuates Chronic Angiotensin II-Induced Hypertension in the Rat
Int. J. Mol. Sci. 2014, 15(12), 22203-22213; doi:10.3390/ijms151222203
Received: 27 October 2014 / Revised: 17 November 2014 / Accepted: 26 November 2014 / Published: 2 December 2014
Cited by 1 | PDF Full-text (1502 KB) | HTML Full-text | XML Full-text
Abstract
The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to
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The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·) scavenging enzyme, in the SFO attenuates chronic AngII-induced hypertension. Herein, we tested the hypothesis that overproduction of O2· in the MnPO is an underlying mechanism in the long-term hypertensive effects of chronic AngII. Adenoviral vectors encoding human CuZnSOD (AdCuZnSOD) or control vector (AdEmpty) were injected directly into the MnPO of rats implanted with aortic telemetric transmitters for recording of arterial pressure. After a 3 day control period of saline infusion, rats were intravenously infused with AngII (10 ng/kg/min) for ten days. Rats over-expressing CuZnSOD (n = 7) in the MnPO had a blood pressure increase of only 6 ± 2 mmHg after ten days of AngII infusion while blood pressure increased 21 ± 4 mmHg in AdEmpty-infected rats (n = 9). These results support the hypothesis that production of O2· in the MnPO contributes to the development of chronic AngII-dependent hypertension. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
Open AccessArticle Role of NADPH Oxidase and Xanthine Oxidase in Mediating Inducible VT/VF and Triggered Activity in a Canine Model of Myocardial Ischemia
Int. J. Mol. Sci. 2014, 15(11), 20079-20100; doi:10.3390/ijms151120079
Received: 23 August 2014 / Revised: 17 October 2014 / Accepted: 21 October 2014 / Published: 4 November 2014
Cited by 2 | PDF Full-text (1170 KB) | HTML Full-text | XML Full-text
Abstract
Background: Ventricular tachycardia or fibrillation (VT/VF) of focal origin due to triggered activity (TA) from delayed afterdepolarizations (DADs) is reproducibly inducible after anterior coronary artery occlusion. Both VT/VF and TA can be blocked by reducing reactive oxygen species (ROS). We tested the hypothesis
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Background: Ventricular tachycardia or fibrillation (VT/VF) of focal origin due to triggered activity (TA) from delayed afterdepolarizations (DADs) is reproducibly inducible after anterior coronary artery occlusion. Both VT/VF and TA can be blocked by reducing reactive oxygen species (ROS). We tested the hypothesis that inhibition of NADPH oxidase and xanthine oxidase would block VT/VF. Methods: 69 dogs received apocynin (APO), 4 mg/kg intraveneously (IV), oxypurinol (OXY), 4 mg/kg IV, or both APO and OXY (BOTH) agents, or saline 3 h after coronary occlusion. Endocardium from ischemic sites (3-D mapping) was sampled for Rac1 (GTP-binding protein in membrane NADPH oxidase) activation or standard microelectrode techniques. Results (mean ± SE, * p < 0.05): VT/VF originating from ischemic zones was blocked by APO in 6/10 *, OXY in 4/9 *, BOTH in 5/8 * or saline in 1/27; 11/16 VT/VFs blocked were focal. In isolated myocardium, TA was blocked by APO (10−6 M) or OXY (10−8 M). Rac1 levels in ischemic endocardium were decreased by APO or OXY. Conclusion: APO and OXY suppressed focal VT/VF due to DADs, but the combination of the drugs was not more effective than either alone. Both drugs inhibited ischemic Rac1 with inhibition by OXY suggesting ROS-induced ROS. The inability to totally prevent VT/VF suggests that other mechanisms also contribute to ischemic VT. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
Open AccessArticle Obligatory Role of Intraluminal O2 in Acute Endothelin-1 and Angiotensin II Signaling to Mediate Endothelial Dysfunction and MAPK Activation in Guinea-Pig Hearts
Int. J. Mol. Sci. 2014, 15(11), 19417-19443; doi:10.3390/ijms151119417
Received: 5 August 2014 / Revised: 30 September 2014 / Accepted: 8 October 2014 / Published: 27 October 2014
Cited by 4 | PDF Full-text (13418 KB) | HTML Full-text | XML Full-text
Abstract
We hypothesized that, due to a cross-talk between cytoplasmic O2-sources and intraluminally expressed xanthine oxidase (XO), intraluminal O2 is instrumental in mediating intraluminal (endothelial dysfunction) and cytosolic (p38 and ERK1/2 MAPKs phosphorylation) manifestations of vascular oxidative stress induced
[...] Read more.
We hypothesized that, due to a cross-talk between cytoplasmic O2-sources and intraluminally expressed xanthine oxidase (XO), intraluminal O2 is instrumental in mediating intraluminal (endothelial dysfunction) and cytosolic (p38 and ERK1/2 MAPKs phosphorylation) manifestations of vascular oxidative stress induced by endothelin-1 (ET-1) and angiotensin II (AT-II). Isolated guinea-pig hearts were subjected to 10-min agonist perfusion causing a burst of an intraluminal O2. ET-1 antagonist, tezosentan, attenuated AT-II-mediated O2, indicating its partial ET-1 mediation. ET-1 and Ang-T (AT-II + tezosentan) triggered intraluminal O2, endothelial dysfunction, MAPKs and p47phox phosphorylation, and NADPH oxidase (Nox) and XO activation. These effects were: (i) prevented by blocking PKC (chelerythrine), Nox (apocynin), mitochondrial ATP-dependent K+ channel (5-HD), complex II (TTFA), and XO (allopurinol); (ii) mimicked by the activation of Nox (NADH); and mitochondria (diazoxide, 3-NPA) and (iii) the effects by NADH were prevented by 5-HD, TTFA and chelerythrine, and those by diazoxide and 3-NPA by apocynin and chelerythrine, suggesting that the agonists coactivate Nox and mitochondria, which further amplify their activity via PKC. The effects by ET-1, Ang-T, NADH, diazoxide, and 3-NPA were opposed by blocking intraluminal O2 (SOD) and XO, and were mimicked by XO activation (hypoxanthine). Apocynin, TTFA, chelerythrine, and SOD opposed the effects by hypoxanthine. In conclusion, oxidative stress by agonists involves cellular inside-out and outside-in signaling in which Nox-mitochondria-PKC system and XO mutually maintain their activities via the intraluminal O2. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
Open AccessArticle TRPV1 Activation Exacerbates Hypoxia/Reoxygenation-Induced Apoptosis in H9C2 Cells via Calcium Overload and Mitochondrial Dysfunction
Int. J. Mol. Sci. 2014, 15(10), 18362-18380; doi:10.3390/ijms151018362
Received: 29 May 2014 / Revised: 27 September 2014 / Accepted: 29 September 2014 / Published: 13 October 2014
Cited by 11 | PDF Full-text (2983 KB) | HTML Full-text | XML Full-text
Abstract
Transient potential receptor vanilloid 1 (TRPV1) channels, which are expressed on sensory neurons, elicit cardioprotective effects during ischemia reperfusion injury by stimulating the release of neuropeptides, namely calcitonin gene-related peptide (CGRP) and substance P (SP). Recent studies show that TRPV1 channels are also
[...] Read more.
Transient potential receptor vanilloid 1 (TRPV1) channels, which are expressed on sensory neurons, elicit cardioprotective effects during ischemia reperfusion injury by stimulating the release of neuropeptides, namely calcitonin gene-related peptide (CGRP) and substance P (SP). Recent studies show that TRPV1 channels are also expressed on cardiomyocytes and can exacerbate air pollutant-induced apoptosis. However, whether these channels present on cardiomyocytes directly modulate cell death and survival pathways during hypoxia/reoxygenation (H/R) injury remains unclear. In the present study, we investigated the role of TRPV1 in H/R induced apoptosis of H9C2 cardiomyocytes. We demonstrated that TRPV1 was indeed expressed in H9C2 cells, and activated by H/R injury. Although neuropeptide release caused by TRPV1 activation on sensory neurons elicits a cardioprotective effect, we found that capsaicin (CAP; a TRPV1 agonist) treatment of H9C2 cells paradoxically enhanced the level of apoptosis by increasing intracellular calcium and mitochondrial superoxide levels, attenuating mitochondrial membrane potential, and inhibiting mitochondrial biogenesis (measured by the expression of ATP synthase β). In contrast, treatment of cells with capsazepine (CPZ; a TRPV1 antagonist) or TRPV1 siRNA attenuated H/R induced-apoptosis. Furthermore, CAP and CPZ treatment revealed a similar effect on cell viability and mitochondrial superoxide production in primary cardiomyocytes. Finally, using both CGRP8–37 (a CGRP receptor antagonist) and RP67580 (a SP receptor antagonist) to exclude the confounding effects of neuropeptides, we confirmed aforementioned detrimental effects as TRPV1−/− mouse hearts exhibited improved cardiac function during ischemia/reperfusion. In summary, direct activation of TRPV1 in myocytes exacerbates H/R-induced apoptosis, likely through calcium overload and associated mitochondrial dysfunction. Our study provides a novel understanding of the role of myocyte TRPV1 channels in ischemia/reperfusion injury that sharply contrasts with its known extracardiac neuronal effects. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
Open AccessArticle Over-Expression of Catalase in Myeloid Cells Confers Acute Protection Following Myocardial Infarction
Int. J. Mol. Sci. 2014, 15(5), 9036-9050; doi:10.3390/ijms15059036
Received: 17 April 2014 / Revised: 12 May 2014 / Accepted: 14 May 2014 / Published: 21 May 2014
Cited by 3 | PDF Full-text (1048 KB) | HTML Full-text | XML Full-text
Abstract
Cardiovascular disease is the leading cause of death in the United States and new treatment options are greatly needed. Oxidative stress is increased following myocardial infarction and levels of antioxidants decrease, causing imbalance that leads to dysfunction. Therapy involving catalase, the endogenous scavenger
[...] Read more.
Cardiovascular disease is the leading cause of death in the United States and new treatment options are greatly needed. Oxidative stress is increased following myocardial infarction and levels of antioxidants decrease, causing imbalance that leads to dysfunction. Therapy involving catalase, the endogenous scavenger of hydrogen peroxide (H2O2), has been met with mixed results. When over-expressed in cardiomyocytes from birth, catalase improves function following injury. When expressed in the same cells in an inducible manner, catalase showed a time-dependent response with no acute benefit, but a chronic benefit due to altered remodeling. In myeloid cells, catalase over-expression reduced angiogenesis during hindlimb ischemia and prevented monocyte migration. In the present study, due to the large inflammatory response following infarction, we examined myeloid-specific catalase over-expression on post-infarct healing. We found a significant increase in catalase levels following infarction that led to a decrease in H2O2 levels, leading to improved acute function. This increase in function could be attributed to reduced infarct size and improved angiogenesis. Despite these initial improvements, there was no improvement in chronic function, likely due to increased fibrosis. These data combined with what has been previously shown underscore the need for temporal, cell-specific catalase delivery as a potential therapeutic option. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)

Review

Jump to: Research

Open AccessReview Redox Roles of Reactive Oxygen Species in Cardiovascular Diseases
Int. J. Mol. Sci. 2015, 16(11), 27770-27780; doi:10.3390/ijms161126059
Received: 17 September 2015 / Revised: 6 November 2015 / Accepted: 11 November 2015 / Published: 20 November 2015
Cited by 40 | PDF Full-text (209 KB) | HTML Full-text | XML Full-text
Abstract
Cardiovascular disease (CVD), a major cause of mortality in the world, has been extensively studied over the past decade. However, the exact mechanism underlying its pathogenesis has not been fully elucidated. Reactive oxygen species (ROS) play a pivotal role in the progression of
[...] Read more.
Cardiovascular disease (CVD), a major cause of mortality in the world, has been extensively studied over the past decade. However, the exact mechanism underlying its pathogenesis has not been fully elucidated. Reactive oxygen species (ROS) play a pivotal role in the progression of CVD. Particularly, ROS are commonly engaged in developing typical characteristics of atherosclerosis, one of the dominant CVDs. This review will discuss the involvement of ROS in atherosclerosis, specifically their effect on inflammation, disturbed blood flow and arterial wall remodeling. Pharmacological interventions target ROS in order to alleviate oxidative stress and CVD symptoms, yet results are varied due to the paradoxical role of ROS in CVD. Lack of effectiveness in clinical trials suggests that understanding the exact role of ROS in the pathophysiology of CVD and developing novel treatments, such as antioxidant gene therapy and nanotechnology-related antioxidant delivery, could provide a therapeutic advance in treating CVDs. While genetic therapies focusing on specific antioxidant expression seem promising in CVD treatments, multiple technological challenges exist precluding its immediate clinical applications. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
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Open AccessReview Diabetic Cardiovascular Disease Induced by Oxidative Stress
Int. J. Mol. Sci. 2015, 16(10), 25234-25263; doi:10.3390/ijms161025234
Received: 1 September 2015 / Revised: 30 September 2015 / Accepted: 30 September 2015 / Published: 23 October 2015
Cited by 68 | PDF Full-text (890 KB) | HTML Full-text | XML Full-text
Abstract
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM). DM can lead to multiple cardiovascular complications, including coronary artery disease (CAD), cardiac hypertrophy, and heart failure (HF). HF represents one of the most common causes
[...] Read more.
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM). DM can lead to multiple cardiovascular complications, including coronary artery disease (CAD), cardiac hypertrophy, and heart failure (HF). HF represents one of the most common causes of death in patients with DM and results from DM-induced CAD and diabetic cardiomyopathy. Oxidative stress is closely associated with the pathogenesis of DM and results from overproduction of reactive oxygen species (ROS). ROS overproduction is associated with hyperglycemia and metabolic disorders, such as impaired antioxidant function in conjunction with impaired antioxidant activity. Long-term exposure to oxidative stress in DM induces chronic inflammation and fibrosis in a range of tissues, leading to formation and progression of disease states in these tissues. Indeed, markers for oxidative stress are overexpressed in patients with DM, suggesting that increased ROS may be primarily responsible for the development of diabetic complications. Therefore, an understanding of the pathophysiological mechanisms mediated by oxidative stress is crucial to the prevention and treatment of diabetes-induced CVD. The current review focuses on the relationship between diabetes-induced CVD and oxidative stress, while highlighting the latest insights into this relationship from findings on diabetic heart and vascular disease. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
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Open AccessReview A Review of the Effect of Diet on Cardiovascular Calcification
Int. J. Mol. Sci. 2015, 16(4), 8861-8883; doi:10.3390/ijms16048861
Received: 29 January 2015 / Revised: 19 March 2015 / Accepted: 7 April 2015 / Published: 21 April 2015
Cited by 11 | PDF Full-text (718 KB) | HTML Full-text | XML Full-text
Abstract
Cardiovascular (CV) calcification is known as sub-clinical atherosclerosis and is recognised as a predictor of CV events and mortality. As yet there is no treatment for CV calcification and conventional CV risk factors are not consistently correlated, leaving clinicians uncertain as to optimum
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Cardiovascular (CV) calcification is known as sub-clinical atherosclerosis and is recognised as a predictor of CV events and mortality. As yet there is no treatment for CV calcification and conventional CV risk factors are not consistently correlated, leaving clinicians uncertain as to optimum management for these patients. For this reason, a review of studies investigating diet and serum levels of macro- and micronutrients was carried out. Although there were few human studies of macronutrients, nevertheless transfats and simple sugars should be avoided, while long chain ω-3 fats from oily fish may be protective. Among the micronutrients, an intake of 800 μg/day calcium was beneficial in those without renal disease or hyperparathyroidism, while inorganic phosphorus from food preservatives and colas may induce calcification. A high intake of magnesium (≥380 mg/day) and phylloquinone (500 μg/day) proved protective, as did a serum 25(OH)D concentration of ≥75 nmol/L. Although oxidative damage appears to be a cause of CV calcification, the antioxidant vitamins proved to be largely ineffective, while supplementation of α-tocopherol may induce calcification. Nevertheless other antioxidant compounds (epigallocatechin gallate from green tea and resveratrol from red wine) were protective. Finally, a homocysteine concentration >12 µmol/L was predictive of CV calcification, although a plasma folate concentration of >39.4 nmol/L could both lower homocysteine and protect against calcification. In terms of a dietary programme, these recommendations indicate avoiding sugar and the transfats and preservatives found in processed foods and drinks and adopting a diet high in oily fish and vegetables. The micronutrients magnesium and vitamin K may be worthy of further investigation as a treatment option for CV calcification. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
Open AccessReview Nitric Oxide and Reactive Oxygen Species in the Pathogenesis of Preeclampsia
Int. J. Mol. Sci. 2015, 16(3), 4600-4614; doi:10.3390/ijms16034600
Received: 12 November 2014 / Revised: 13 January 2015 / Accepted: 15 February 2015 / Published: 2 March 2015
Cited by 31 | PDF Full-text (975 KB) | HTML Full-text | XML Full-text
Abstract
Preeclampsia (PE) is characterized by disturbed extravillous trophoblast migration toward uterine spiral arteries leading to increased uteroplacental vascular resistance and by vascular dysfunction resulting in reduced systemic vasodilatory properties. Its pathogenesis is mediated by an altered bioavailability of nitric oxide (NO) and tissue
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Preeclampsia (PE) is characterized by disturbed extravillous trophoblast migration toward uterine spiral arteries leading to increased uteroplacental vascular resistance and by vascular dysfunction resulting in reduced systemic vasodilatory properties. Its pathogenesis is mediated by an altered bioavailability of nitric oxide (NO) and tissue damage caused by increased levels of reactive oxygen species (ROS). Furthermore, superoxide (O2) rapidly inactivates NO and forms peroxynitrite (ONOO). It is known that ONOO accumulates in the placental tissues and injures the placental function in PE. In addition, ROS could stimulate platelet adhesion and aggregation leading to intravascular coagulopathy. ROS-induced coagulopathy causes placental infarction and impairs the uteroplacental blood flow in PE. The disorders could lead to the reduction of oxygen and nutrients required for normal fetal development resulting in fetal growth restriction. On the other hand, several antioxidants scavenge ROS and protect tissues against oxidative damage. Placental antioxidants including catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) protect the vasculature from ROS and maintain the vascular function. However, placental ischemia in PE decreases the antioxidant activity resulting in further elevated oxidative stress, which leads to the appearance of the pathological conditions of PE including hypertension and proteinuria. Oxidative stress is defined as an imbalance between ROS and antioxidant activity. This review provides new insights about roles of oxidative stress in the pathophysiology of PE. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
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Open AccessReview Pathogenesis of Target Organ Damage in Hypertension: Role of Mitochondrial Oxidative Stress
Int. J. Mol. Sci. 2015, 16(1), 823-839; doi:10.3390/ijms16010823
Received: 18 November 2014 / Accepted: 26 December 2014 / Published: 31 December 2014
Cited by 35 | PDF Full-text (1201 KB) | HTML Full-text | XML Full-text
Abstract
Hypertension causes target organ damage (TOD) that involves vasculature, heart, brain and kidneys. Complex biochemical, hormonal and hemodynamic mechanisms are involved in the pathogenesis of TOD. Common to all these processes is an increased bioavailability of reactive oxygen species (ROS). Both in vitro
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Hypertension causes target organ damage (TOD) that involves vasculature, heart, brain and kidneys. Complex biochemical, hormonal and hemodynamic mechanisms are involved in the pathogenesis of TOD. Common to all these processes is an increased bioavailability of reactive oxygen species (ROS). Both in vitro and in vivo studies explored the role of mitochondrial oxidative stress as a mechanism involved in the pathogenesis of TOD in hypertension, especially focusing on atherosclerosis, heart disease, renal failure, cerebrovascular disease. Both dysfunction of mitochondrial proteins, such as uncoupling protein-2 (UCP2), superoxide dismutase (SOD) 2, peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), calcium channels, and the interaction between mitochondria and other sources of ROS, such as NADPH oxidase, play an important role in the development of endothelial dysfunction, cardiac hypertrophy, renal and cerebral damage in hypertension. Commonly used anti-hypertensive drugs have shown protective effects against mitochondrial-dependent oxidative stress. Notably, few mitochondrial proteins can be considered therapeutic targets on their own. In fact, antioxidant therapies specifically targeted at mitochondria represent promising strategies to reduce mitochondrial dysfunction and related hypertensive TOD. In the present article, we discuss the role of mitochondrial oxidative stress as a contributing factor to hypertensive TOD development. We also provide an overview of mitochondria-based treatment strategies that may reveal useful to prevent TOD and reduce its progression. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
Open AccessReview Chlamydia pneumoniae and Oxidative Stress in Cardiovascular Disease: State of the Art and Prevention Strategies
Int. J. Mol. Sci. 2015, 16(1), 724-735; doi:10.3390/ijms16010724
Received: 4 November 2014 / Accepted: 26 December 2014 / Published: 30 December 2014
Cited by 11 | PDF Full-text (2840 KB) | HTML Full-text | XML Full-text
Abstract
Chlamydia pneumoniae, a pathogenic bacteria responsible for respiratory tract infections, is known as the most implicated infectious agent in atherosclerotic cardiovascular diseases (CVDs). Accumulating evidence suggests that C. pneumoniae-induced oxidative stress may play a critical role in the pathogenesis of CVDs.
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Chlamydia pneumoniae, a pathogenic bacteria responsible for respiratory tract infections, is known as the most implicated infectious agent in atherosclerotic cardiovascular diseases (CVDs). Accumulating evidence suggests that C. pneumoniae-induced oxidative stress may play a critical role in the pathogenesis of CVDs. Indeed, the overproduction of reactive oxygen species (ROS) within macrophages, endothelial cells, platelets and vascular smooth muscle cells (VSMCs) after C. pneumoniae exposure, has been shown to cause low density lipoprotein oxidation, foam cell formation, endothelial dysfunction, platelet adhesion and aggregation, and VSMC proliferation and migration, all responsible for the typical pathological changes of atherosclerotic plaque. The aim of this review is to improve our insight into C. pneumoniae-induced oxidative stress in order to suggest potential strategies for CVD prevention. Several antioxidants, acting on multi-enzymatic targets related to ROS production induced by C. pneumoniae, have been discussed. A future strategy for the prevention of C. pneumoniae-associated CVDs will be to target chlamydial HSP60, involved in oxidative stress. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
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Open AccessReview Lipoprotein-Associated Oxidative Stress: A New Twist to the Postprandial Hypothesis
Int. J. Mol. Sci. 2015, 16(1), 401-419; doi:10.3390/ijms16010401
Received: 18 November 2014 / Accepted: 16 December 2014 / Published: 26 December 2014
Cited by 11 | PDF Full-text (922 KB) | HTML Full-text | XML Full-text
Abstract
Oxidative stress is recognized as one of the primary processes underlying the initiation and progression of atherosclerotic vascular disease. Under physiological conditions, the balance between reactive oxygen species (ROS) generation and ROS scavenging is tightly controlled. As part of normal cellular metabolism, regulated
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Oxidative stress is recognized as one of the primary processes underlying the initiation and progression of atherosclerotic vascular disease. Under physiological conditions, the balance between reactive oxygen species (ROS) generation and ROS scavenging is tightly controlled. As part of normal cellular metabolism, regulated oxidative stress is responsible for a variety of cellular responses. Excess generation of ROS that could not be compensated by antioxidant system has been suggested to be responsible for a number of pathological conditions. Due to their short biological half-lives, direct measurement of ROS is not available and surrogate measures are commonly used. Plasma lipoproteins, by virtue of their close interactions with endothelial cells in the vasculature and the susceptibility of their surface lipids to oxidative modification, are perfect biological sensors of oxidative stress in the arterial wall. In particular, with each consumed meal, triglyceride-rich lipoproteins, secreted by the intestine into the circulation, are responsible for the delivery of 20–40 grams of fat to the peripheral tissues. This flux of dietary lipids is accompanied by concomitant increases in glucose, insulin and other meal-associated metabolites. The contribution of postprandial lipemia to the pathogenesis of atherosclerosis has been previously suggested by several lines of investigation. We have extended this hypothesis by demonstrating the acute generation of oxidative epitopes on plasma lipoproteins as well as transient changes in the oxidative susceptibility of plasma lipoproteins. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
Open AccessReview The Role of Reactive Oxygen Species in Microvascular Remodeling
Int. J. Mol. Sci. 2014, 15(12), 23792-23835; doi:10.3390/ijms151223792
Received: 30 October 2014 / Revised: 5 December 2014 / Accepted: 10 December 2014 / Published: 19 December 2014
Cited by 7 | PDF Full-text (1139 KB) | HTML Full-text | XML Full-text
Abstract
The microcirculation is a portion of the vascular circulatory system that consists of resistance arteries, arterioles, capillaries and venules. It is the place where gases and nutrients are exchanged between blood and tissues. In addition the microcirculation is the major contributor to blood
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The microcirculation is a portion of the vascular circulatory system that consists of resistance arteries, arterioles, capillaries and venules. It is the place where gases and nutrients are exchanged between blood and tissues. In addition the microcirculation is the major contributor to blood flow resistance and consequently to regulation of blood pressure. Therefore, structural remodeling of this section of the vascular tree has profound implications on cardiovascular pathophysiology. This review is focused on the role that reactive oxygen species (ROS) play on changing the structural characteristics of vessels within the microcirculation. Particular attention is given to the resistance arteries and the functional pathways that are affected by ROS in these vessels and subsequently induce vascular remodeling. The primary sources of ROS in the microcirculation are identified and the effects of ROS on other microcirculatory remodeling phenomena such as rarefaction and collateralization are briefly reviewed. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
Open AccessReview Looking into a Conceptual Framework of ROS–miRNA–Atrial Fibrillation
Int. J. Mol. Sci. 2014, 15(12), 21754-21776; doi:10.3390/ijms151221754
Received: 20 October 2014 / Revised: 17 November 2014 / Accepted: 19 November 2014 / Published: 26 November 2014
Cited by 7 | PDF Full-text (1147 KB) | HTML Full-text | XML Full-text
Abstract
Atrial fibrillation (AF) has been recognized as a major cause of cardiovascular-related morbidity and mortality. MicroRNAs (miRNAs) represent recent additions to the collection of biomolecules involved in arrhythmogenesis. Reactive oxygen species (ROS) have been independently linked to both AF and miRNA regulation. However,
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Atrial fibrillation (AF) has been recognized as a major cause of cardiovascular-related morbidity and mortality. MicroRNAs (miRNAs) represent recent additions to the collection of biomolecules involved in arrhythmogenesis. Reactive oxygen species (ROS) have been independently linked to both AF and miRNA regulation. However, no attempts have been made to investigate the possibility of a framework composed of ROS–miRNA–AF that is related to arrhythmia development. Therefore, this review was designed as an attempt to offer a new approach to understanding AF pathogenesis. The aim of this review was to find and to summarize possible connections that exist among AF, miRNAs and ROS to understand the interactions among the molecular entities underlying arrhythmia development in the hopes of finding unappreciated mechanisms of AF. These findings may lead us to innovative therapies for AF, which can be a life-threatening heart condition. A systemic literature review indicated that miRNAs associated with AF might be regulated by ROS, suggesting the possibility that miRNAs translate cellular stressors, such as ROS, into AF pathogenesis. Further studies with a more appropriate experimental design to either prove or disprove the existence of an ROS–miRNA–AF framework are strongly encouraged. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
Open AccessReview Exploring the Role of Paraoxonases in the Pathogenesis of Coronary Artery Disease: A Systematic Review
Int. J. Mol. Sci. 2014, 15(11), 20997-21010; doi:10.3390/ijms151120997
Received: 23 October 2014 / Accepted: 10 November 2014 / Published: 14 November 2014
Cited by 11 | PDF Full-text (521 KB) | HTML Full-text | XML Full-text
Abstract
Paraoxonases (PON) are three enzymes (PON1, PON2 and PON3) that play a role in the organism’s antioxidant system; alterations in which are associated with diseases involving oxidative stress. In this review, we summarize the evidence of PON related to the pathogenesis of coronary
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Paraoxonases (PON) are three enzymes (PON1, PON2 and PON3) that play a role in the organism’s antioxidant system; alterations in which are associated with diseases involving oxidative stress. In this review, we summarize the evidence of PON related to the pathogenesis of coronary artery disease (CAD) and atherosclerosis. We searched three electronic databases (PubMed, Scopus and Cochrane Database) with no date limit. All of the articles selected investigated PON enzymatic activity and/or PON gene polymorphisms. The selection focused on PON in relation to atherosclerosis, CAD and myocardial infarction. The exclusion criteria were a sample size <100 patients, non-human studies, editorials and systematic reviews without restrictions on the country of origin. With these criteria, we identified thirty-five prospective studies published between 1986 and 2014 with a total of 28,164 participants. The relationship between PON gene polymorphisms and CAD was not conclusive, but most studies support the concept that alterations in PON1 enzymatic activity levels do influence atheroma formation. Conversely, relationships between PON2 and PON3 vs. CAD have not been extensively investigated. Our review of the current data concludes that the bases of paraoxonases involvement in atherosclerosis are poorly understood and that this issue requires future comprehensive, multi-centered studies. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
Open AccessReview Glutathionylation of the L-type Ca2+ Channel in Oxidative Stress-Induced Pathology of the Heart
Int. J. Mol. Sci. 2014, 15(10), 19203-19225; doi:10.3390/ijms151019203
Received: 27 August 2014 / Revised: 29 September 2014 / Accepted: 2 October 2014 / Published: 22 October 2014
Cited by 6 | PDF Full-text (2308 KB) | HTML Full-text | XML Full-text
Abstract
There is mounting evidence to suggest that protein glutathionylation is a key process contributing to the development of pathology. Glutathionylation occurs as a result of posttranslational modification of a protein and involves the addition of a glutathione moiety at cysteine residues. Such modification
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There is mounting evidence to suggest that protein glutathionylation is a key process contributing to the development of pathology. Glutathionylation occurs as a result of posttranslational modification of a protein and involves the addition of a glutathione moiety at cysteine residues. Such modification can occur on a number of proteins, and exerts a variety of functional consequences. The L-type Ca2+ channel has been identified as a glutathionylation target that participates in the development of cardiac pathology. Ca2+ influx via the L-type Ca2+ channel increases production of mitochondrial reactive oxygen species (ROS) in cardiomyocytes during periods of oxidative stress. This induces a persistent increase in channel open probability, and the resulting constitutive increase in Ca2+ influx amplifies the cross-talk between the mitochondria and the channel. Novel strategies utilising targeted peptide delivery to uncouple mitochondrial ROS and Ca2+ flux via the L-type Ca2+ channel following ischemia-reperfusion have delivered promising results, and have proven capable of restoring appropriate mitochondrial function in myocytes and in vivo. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
Open AccessReview Glycemic Variability and Oxidative Stress: A Link between Diabetes and Cardiovascular Disease?
Int. J. Mol. Sci. 2014, 15(10), 18381-18406; doi:10.3390/ijms151018381
Received: 26 August 2014 / Revised: 16 September 2014 / Accepted: 28 September 2014 / Published: 13 October 2014
Cited by 30 | PDF Full-text (980 KB) | HTML Full-text | XML Full-text
Abstract
Diabetes is associated with a two to three-fold increase in risk of cardiovascular disease. However, intensive glucose-lowering therapy aiming at reducing HbA1c to a near-normal level failed to suppress cardiovascular events in recent randomized controlled trials. HbA1c reflects average glucose level rather than
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Diabetes is associated with a two to three-fold increase in risk of cardiovascular disease. However, intensive glucose-lowering therapy aiming at reducing HbA1c to a near-normal level failed to suppress cardiovascular events in recent randomized controlled trials. HbA1c reflects average glucose level rather than glycemic variability. In in vivo and in vitro studies, glycemic variability has been shown to be associated with greater reactive oxygen species production and vascular damage, compared to chronic hyperglycemia. These findings suggest that management of glycemic variability may reduce cardiovascular disease in patients with diabetes; however, clinical studies have shown conflicting results. This review summarizes the current knowledge on glycemic variability and oxidative stress, and discusses the clinical implications. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
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Open AccessReview Restoration of Asymmetric Dimethylarginine–Nitric Oxide Balance to Prevent the Development of Hypertension
Int. J. Mol. Sci. 2014, 15(7), 11773-11782; doi:10.3390/ijms150711773
Received: 27 May 2014 / Revised: 24 June 2014 / Accepted: 27 June 2014 / Published: 2 July 2014
Cited by 15 | PDF Full-text (883 KB) | HTML Full-text | XML Full-text
Abstract
Despite the use of extensive antihypertensive therapy in patients with hypertension, little attention has been paid to early identification and intervention of individuals at risk for developing hypertension. The imbalance between nitric oxide (NO) and reactive oxygen species (ROS) resulting in oxidative stress
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Despite the use of extensive antihypertensive therapy in patients with hypertension, little attention has been paid to early identification and intervention of individuals at risk for developing hypertension. The imbalance between nitric oxide (NO) and reactive oxygen species (ROS) resulting in oxidative stress has been implicated in the pathophysiology of hypertension. NO deficiency can precede the development of hypertension. Asymmetric dimethylarginine (ADMA) can inhibit nitric oxide synthase (NOS) and regulate local NO/ROS balance. Emerging evidence supports the hypothesis that ADMA-induced NO–ROS imbalance is involved in the development and progression of hypertension. Thus, this review summarizes recent experimental approaches to restore ADMA–NO balance in order to prevent the development of hypertension. Since hypertension might originate in early life, we also discuss the putative role of the ADMA–NO pathway in programmed hypertension. Better understanding of manipulations of the ADMA–NO pathway prior to hypertension in favor of NO will pave the way for the development of more effective medicine for the treatment prehypertension and programmed hypertension. However, more studies are needed to confirm the clinical benefit of these interventions. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
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Open AccessReview Endothelial Dysfunction in Chronic Inflammatory Diseases
Int. J. Mol. Sci. 2014, 15(7), 11324-11349; doi:10.3390/ijms150711324
Received: 9 May 2014 / Revised: 23 May 2014 / Accepted: 6 June 2014 / Published: 25 June 2014
Cited by 97 | PDF Full-text (1016 KB) | HTML Full-text | XML Full-text
Abstract
Chronic inflammatory diseases are associated with accelerated atherosclerosis and increased risk of cardiovascular diseases (CVD). As the pathogenesis of atherosclerosis is increasingly recognized as an inflammatory process, similarities between atherosclerosis and systemic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel diseases, lupus, psoriasis,
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Chronic inflammatory diseases are associated with accelerated atherosclerosis and increased risk of cardiovascular diseases (CVD). As the pathogenesis of atherosclerosis is increasingly recognized as an inflammatory process, similarities between atherosclerosis and systemic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel diseases, lupus, psoriasis, spondyloarthritis and others have become a topic of interest. Endothelial dysfunction represents a key step in the initiation and maintenance of atherosclerosis and may serve as a marker for future risk of cardiovascular events. Patients with chronic inflammatory diseases manifest endothelial dysfunction, often early in the course of the disease. Therefore, mechanisms linking systemic inflammatory diseases and atherosclerosis may be best understood at the level of the endothelium. Multiple factors, including circulating inflammatory cytokines, TNF-α (tumor necrosis factor-α), reactive oxygen species, oxidized LDL (low density lipoprotein), autoantibodies and traditional risk factors directly and indirectly activate endothelial cells, leading to impaired vascular relaxation, increased leukocyte adhesion, increased endothelial permeability and generation of a pro-thrombotic state. Pharmacologic agents directed against TNF-α-mediated inflammation may decrease the risk of endothelial dysfunction and cardiovascular disease in these patients. Understanding the precise mechanisms driving endothelial dysfunction in patients with systemic inflammatory diseases may help elucidate the pathogenesis of atherosclerosis in the general population. Full article
(This article belongs to the Special Issue Oxidative Stress in Cardiovascular Disease 2015)
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