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Special Issue "Hypertension and Cardiovascular Diseases: From Etiopathogenesis to Potential Therapeutic Targets"

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 2021).

Special Issue Editors

Dr. Iveta Bernatova
E-Mail Website
Guest Editor
Department of Experimental Hypertension, Institute of Normal and Pathological Physiology, Centre of Experimental Medicine of Slovak Academy of Sciences, Bratislava, Slovakia
Interests: experimental hypertension; prehypertension; nitric oxide; social stress; vascular function; aging; iron metabolism; oxidative stress; natural polyphenols
Special Issues and Collections in MDPI journals
Dr. Monika Bartekova
E-Mail Website
Guest Editor
1. Department of Cardiovascular Physiology and Pathophysiology, Institute for Heart Research, Centre of Experimental Medicine of Slovak Academy of Sciences, Bratislava, Slovakia
2. Institute of Physiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia
Interests: coronary artery disease; myocardial infarction; cardioprotective interventions; ischemic conditioning; experimental hypertension; diabetes mellitus; hyperlipidaemia; natural antioxidants; flavonoids; extracellular vesicles; non-coding RNAs
Special Issues and Collections in MDPI journals
Dr. Silvia Liskova
E-Mail Website
Guest Editor
1. Department of Experimental Hypertension, Institute of Normal and Pathological Physiology, Centre of Experimental Medicine of Slovak Academy of Sciences, Bratislava, Slovakia
2. Institute of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Comenius University, Bratislava, Slovakia
Interests: hypertension; diabetes mellitus; hypercholesterolemia; vascular physiology; ion channels and ion homeostatis; endothelium; endothelium-derived factors; cyclooxygenase pathway; sympathetic nervous system; ontogenetic development
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Cardiovascular diseases (CVDs), including coronary heart disease and arterial hypertension, are the top cause of death worldwide, and arterial hypertension per se remains the major preventable cause of CVDs. The prevalence of hypertension increases with age, but prehypertension is common among the young population. Risk factors of CVDs consist of non-modifiable factors (genetic composition, age, sex, race) and modifiable factors such as smoking, unhealthy diet, physical inactivity, and stress. CVDs are often associated with dyslipidemia, type two diabetes mellitus, hypercholesterolemia, and obesity. Hypertension, heart disease, and diabetes mellitus are also medical conditions negatively affecting the prognosis of patients infected with SARS-CoV-2.

The pathophysiology of CVDs involves multiple factors, amongst them alterations in the sympathetic nervous system, renin-angiotensin-aldosterone system, endothelial dysfunction, inflammation, and oxidative stress. In addition, alterations in intracellular and extracellular signaling pathways may be involved. Specifically, various nuclear factors and receptors involved in the regulation of antioxidant defense, nitric oxide production, inflammation, energy, and/or iron metabolism provide new targets for the prevention and treatment of CVDs and comorbid diseases.

This Special Issue will focus on novel mechanisms in the etiopathogenesis of arterial hypertension and coronary heart disease, prevention, and potential therapeutic targets of CVDs. Original research articles, reviews, short communications, and epidemiological studies are welcome.

This Special Issue is jointly organized between IJMS and Biomedicines. In accordance with the Aims and Scope of these journals, articles covering molecular studies can be submitted to IJMS, whereas articles presenting more clinical content can be submitted to Biomedicines.

Dr. Iveta Bernatova
Dr. Monika Bartekova
Dr. Silvia Liskova
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • arterial hypertension
  • coronary heart disease
  • endothelium
  • inflammation
  • oxidative stress
  • gasotransmitters
  • receptors and ion channels
  • transcriptional factors
  • non-coding RNA
  • gene expression
  • nuclear factors and receptors
  • cardioprotection
  • prevention and treatment: natural polyphenols, antioxidants, gut microbiota

Published Papers (11 papers)

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Research

Jump to: Review

Article
Helium Conditioning Increases Cardiac Fibroblast Migration Which Effect Is Not Propagated via Soluble Factors or Extracellular Vesicles
Int. J. Mol. Sci. 2021, 22(19), 10504; https://doi.org/10.3390/ijms221910504 - 29 Sep 2021
Viewed by 332
Abstract
Helium inhalation induces cardioprotection against ischemia/reperfusion injury, the cellular mechanism of which remains not fully elucidated. Extracellular vesicles (EVs) are cell-derived, nano-sized membrane vesicles which play a role in cardioprotective mechanisms, but their function in helium conditioning (HeC) has not been studied so [...] Read more.
Helium inhalation induces cardioprotection against ischemia/reperfusion injury, the cellular mechanism of which remains not fully elucidated. Extracellular vesicles (EVs) are cell-derived, nano-sized membrane vesicles which play a role in cardioprotective mechanisms, but their function in helium conditioning (HeC) has not been studied so far. We hypothesized that HeC induces fibroblast-mediated cardioprotection via EVs. We isolated neonatal rat cardiac fibroblasts (NRCFs) and exposed them to glucose deprivation and HeC rendered by four cycles of 95% helium + 5% CO2 for 1 h, followed by 1 h under normoxic condition. After 40 h of HeC, NRCF activation was analyzed with a Western blot (WB) and migration assay. From the cell supernatant, medium extracellular vesicles (mEVs) were isolated with differential centrifugation and analyzed with WB and nanoparticle tracking analysis. The supernatant from HeC-treated NRCFs was transferred to naïve NRCFs or immortalized human umbilical vein endothelial cells (HUVEC-TERT2), and a migration and angiogenesis assay was performed. We found that HeC accelerated the migration of NRCFs and did not increase the expression of fibroblast activation markers. HeC tended to decrease mEV secretion of NRCFs, but the supernatant of HeC or the control NRCFs did not accelerate the migration of naïve NRCFs or affect the angiogenic potential of HUVEC-TERT2. In conclusion, HeC may contribute to cardioprotection by increasing fibroblast migration but not by releasing protective mEVs or soluble factors from cardiac fibroblasts. Full article
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Article
Analysis of Immune Associated Co-Expression Networks Reveals Immune-Related Long Non-Coding RNAs during MI in the Presence and Absence of HDC
Int. J. Mol. Sci. 2021, 22(14), 7401; https://doi.org/10.3390/ijms22147401 - 09 Jul 2021
Viewed by 564
Abstract
Myocardial infarction (MI) is one of the most common cardiovascular diseases. Although previous studies have shown that histidine decarboxylase (HDC), a histamine-synthesizing enzyme, is involved in the stress response and heart remodeling after MI, the mechanism underlying it remains unclear. In this study, [...] Read more.
Myocardial infarction (MI) is one of the most common cardiovascular diseases. Although previous studies have shown that histidine decarboxylase (HDC), a histamine-synthesizing enzyme, is involved in the stress response and heart remodeling after MI, the mechanism underlying it remains unclear. In this study, using Hdc-deficient mice (Hdc−/− mice), we established an acute myocardial infarction mouse model to explore the potential roles of Hdc/histamine in cardiac immune responses. Comprehensive analysis was performed on the transcriptomes of infarcted hearts. Differentially expressed gene (DEG) analysis identified 2126 DEGs in Hdc-deficient groups and 1013 in histamine-treated groups. Immune related pathways were enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then we used the ssGSEA algorithm to evaluate 22 kinds of infiltrated immunocytes, which indicated that myeloid cells and T memory/follicular helper cells were tightly regulated by Hdc/histamine post MI. The relationships of lncRNAs and the Gene Ontology (GO) functions of protein-coding RNAs and immunocytes were dissected in networks to unveil immune-associated lncRNAs and their roles in immune modulation after MI. Finally, we screened out and verified four lncRNAs, which were closely implicated in tuning the immune responses after MI, including ENSMUST00000191157, ENSMUST00000180693 (PTPRE-AS1), and ENSMUST-00000182785. Our study highlighted the HDC-regulated myeloid cells as a driving force contributing to the government of transmission from innate immunocytes to adaptive immunocytes in the progression of the injury response after MI. We identified the potential role of the Hdc/histamine-lncRNAs network in regulating cardiac immune responses, which may provide novel promising therapeutic targets for further promoting the treatment of ischemic heart disease. Full article
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Article
The Role of Tenascin C in Cardiac Reverse Remodeling Following Banding–Debanding of the Ascending Aorta
Int. J. Mol. Sci. 2021, 22(4), 2023; https://doi.org/10.3390/ijms22042023 - 18 Feb 2021
Cited by 1 | Viewed by 961
Abstract
Background: Tenascin-C (TN-C) plays a maladaptive role in left ventricular (LV) hypertrophy following pressure overload. However, the role of TN-C in LV regression following mechanical unloading is unknown. Methods: LV hypertrophy was induced by transverse aortic constriction for 10 weeks followed by debanding [...] Read more.
Background: Tenascin-C (TN-C) plays a maladaptive role in left ventricular (LV) hypertrophy following pressure overload. However, the role of TN-C in LV regression following mechanical unloading is unknown. Methods: LV hypertrophy was induced by transverse aortic constriction for 10 weeks followed by debanding for 2 weeks in wild type (Wt) and TN-C knockout (TN-C KO) mice. Cardiac function was assessed by serial magnetic resonance imaging. The expression of fibrotic markers and drivers (angiotensin-converting enzyme-1, ACE-1) was determined in LV tissue as well as human cardiac fibroblasts (HCFs) after TN-C treatment. Results: Chronic pressure overload resulted in a significant decline in cardiac function associated with LV dilation as well as upregulation of TN-C, collagen 1 (Col 1), and ACE-1 in Wt as compared to TN-C KO mice. Reverse remodeling in Wt mice partially improved cardiac function and fibrotic marker expression; however, TN-C protein expression remained unchanged. In HCF, TN-C strongly induced the upregulation of ACE 1 and Col 1. Conclusions: Pressure overload, when lasting long enough to induce HF, has less potential for reverse remodeling in mice. This may be due to significant upregulation of TN-C expression, which stimulates ACE 1, Col 1, and alpha-smooth muscle actin (α-SMA) upregulation in fibroblasts. Consequently, addressing TN-C in LV hypertrophy might open a new window for future therapeutics. Full article
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Article
Circulating Total Cell-Free DNA Levels Are Increased in Hypertensive Disorders of Pregnancy and Associated with Prohypertensive Factors and Adverse Clinical Outcomes
Int. J. Mol. Sci. 2021, 22(2), 564; https://doi.org/10.3390/ijms22020564 - 08 Jan 2021
Cited by 2 | Viewed by 734
Abstract
Previous studies have described increased circulating cell-free DNA (cfDNA) in hypertensive disorders of pregnancy (HDP). Here, we aimed first to confirm this information using a simple, but sensible fluorescent assay, and second to investigate whether total cfDNA is associated with circulating factors known [...] Read more.
Previous studies have described increased circulating cell-free DNA (cfDNA) in hypertensive disorders of pregnancy (HDP). Here, we aimed first to confirm this information using a simple, but sensible fluorescent assay, and second to investigate whether total cfDNA is associated with circulating factors known to be linked to the pathophysiology of HDP as well as with poor maternal-fetal outcomes. We studied 98 women with healthy pregnancies (HP), 88 with gestational hypertension (GH), and 91 with preeclampsia (PE). Total DNA was extracted from plasma using the QIAamp DNA blood mini kit and quantified using Quant-iT™ PicoGreen® dsDNA fluorescent detection kit. We found higher total cfDNA levels in GH and PE (197.0 and 174.2 ng/mL, respectively) than in HP (140.5 ng/mL; both p < 0.0001). Interestingly, total cfDNA levels were elevated in both male and female-bearing pregnancies diagnosed with either HDP, and in more severe versus less severe HDP cases, as classified according to responsiveness to antihypertensive therapy. In addition, total cfDNA was independently associated with HDP, and a cutoff concentration of 160 ng/mL provided appropriate sensitivity and specificity values for diagnosing GH and PE compared to HP (70–85%, both p < 0.0001). Moreover, high total cfDNA was associated with adverse clinical outcomes (high blood pressure, low platelet count, preterm delivery, fetal growth restriction) and high prohypertensive factors (sFLT-1, sEndoglin, MMP-2). These findings represent a step towards to the establishment of cfDNA as a diagnostic tool and the need to understand its role in HDP. Full article
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Article
A Sex-Specific Role of Endothelial Sirtuin 3 on Blood Pressure and Diastolic Dysfunction in Female Mice
Int. J. Mol. Sci. 2020, 21(24), 9744; https://doi.org/10.3390/ijms21249744 - 21 Dec 2020
Cited by 1 | Viewed by 752
Abstract
Background: Heart failure with preserved ejection fraction (HFpEF) is characterized by a diastolic dysfunction and is highly prevalent in aged women. Our study showed that ablation of endothelial Sirtuin 3 (SIRT3) led to diastolic dysfunction in male mice. However, the sex-specific role of [...] Read more.
Background: Heart failure with preserved ejection fraction (HFpEF) is characterized by a diastolic dysfunction and is highly prevalent in aged women. Our study showed that ablation of endothelial Sirtuin 3 (SIRT3) led to diastolic dysfunction in male mice. However, the sex-specific role of endothelial SIRT3 deficiency on blood pressure and diastolic function in female mice remains to be investigated. Methods and Results: In this study, we demonstrate that the ablation of endothelial SIRT3 in females elevated blood pressure as compared with control female mice. Diastolic function measurement also showed that the isovolumic relaxation time (IVRT) and myocardial performance index (MPI) were significantly increased, whereas the E’ velocity/A’ velocity (E’/A’) ratio was reduced in the endothelial-specific SIRT3 knockout (SIRT3 ECKO) female mice. To further investigate the regulatory role of endothelial SIRT3 on blood pressure and diastolic dysfunction in metabolic stress, SIRT3 ECKO female mice were fed a normal diet and high-fat diet (HFD) for 20 weeks. The knockout of endothelial SIRT3 resulted in an increased blood pressure in female mice fed with an HFD. Intriguingly, SIRT3 ECKO female mice + HFD exhibited impaired coronary flow reserve (CFR) and more severe diastolic dysfunction as evidenced by an elevated IVRT as compared with control female mice + HFD. In addition, female SIRT3 ECKO mice had higher blood pressure and diastolic dysfunction as compared to male SIRT3 ECKO mice. Moreover, female SIRT3 ECKO mice + HFD had an impaired CFR and diastolic dysfunction as compared to male SIRT3 ECKO mice + HFD. Conclusions: These results implicate a sex-specific role of endothelial SIRT3 in regulating blood pressure and diastolic function in mice. Deficiency of endothelial SIRT3 may be responsible for a diastolic dysfunction in aged female. Full article
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Article
Nox2 Upregulation and p38α MAPK Activation in Right Ventricular Hypertrophy of Rats Exposed to Long-Term Chronic Intermittent Hypobaric Hypoxia
Int. J. Mol. Sci. 2020, 21(22), 8576; https://doi.org/10.3390/ijms21228576 - 13 Nov 2020
Viewed by 766
Abstract
One of the consequences of high altitude (hypobaric hypoxia) exposure is the development of right ventricular hypertrophy (RVH). One particular type of exposure is long-term chronic intermittent hypobaric hypoxia (CIH); the molecular alterations in RVH in this particular condition are less known. Studies [...] Read more.
One of the consequences of high altitude (hypobaric hypoxia) exposure is the development of right ventricular hypertrophy (RVH). One particular type of exposure is long-term chronic intermittent hypobaric hypoxia (CIH); the molecular alterations in RVH in this particular condition are less known. Studies show an important role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex-induced oxidative stress and protein kinase activation in different models of cardiac hypertrophy. The aim was to determine the oxidative level, NADPH oxidase expression and MAPK activation in rats with RVH induced by CIH. Male Wistar rats were randomly subjected to CIH (2 days hypoxia/2 days normoxia; n = 10) and normoxia (NX; n = 10) for 30 days. Hypoxia was simulated with a hypobaric chamber. Measurements in the RV included the following: hypertrophy, Nox2, Nox4, p22phox, LOX-1 and HIF-1α expression, lipid peroxidation and H2O2 concentration, and p38α and Akt activation. All CIH rats developed RVH and showed an upregulation of LOX-1, Nox2 and p22phox and an increase in lipid peroxidation, HIF-1α stabilization and p38α activation. Rats with long-term CIH-induced RVH clearly showed Nox2, p22phox and LOX-1 upregulation and increased lipid peroxidation, HIF-1α stabilization and p38α activation. Therefore, these molecules may be considered new targets in CIH-induced RVH. Full article
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Article
Programmed Cell Death in the Left and Right Ventricle of the Late Phase of Post-Infarction Heart Failure
Int. J. Mol. Sci. 2020, 21(20), 7782; https://doi.org/10.3390/ijms21207782 - 21 Oct 2020
Viewed by 685
Abstract
While necroptosis has been shown to contribute to the pathogenesis of post-infarction heart failure (HF), the role of autophagy remains unclear. Likewise, linkage between these two cell death modalities has not been sufficiently investigated. HF was induced by 60-min left coronary occlusion in [...] Read more.
While necroptosis has been shown to contribute to the pathogenesis of post-infarction heart failure (HF), the role of autophagy remains unclear. Likewise, linkage between these two cell death modalities has not been sufficiently investigated. HF was induced by 60-min left coronary occlusion in adult Wistar rats and heart function was assessed 6 weeks later followed by immunoblotting analysis of necroptotic and autophagic proteins in both the left (LV) and right ventricle (RV). HF had no effect on RIP1 and RIP3 expression. PhosphoSer229-RIP3, acting as a pro-necroptotic signal, was increased in LV while deceased in RV of failing hearts. Total MLKL was elevated in RV only. Decrease in pSer555-ULK1, increase in pSer473-Akt and no significant elevation in beclin-1 and LC3-II/I ratio indicated rather a lowered rate of autophagy in LV. No beclin-1 upregulation and decreased LC3 processing also suggested the inhibition of both autophagosome formation and maturation in RV of failing hearts. In contrast, p89 PARP1 fragment, a marker of executed apoptosis, was increased in RV only. This is the first study showing a different signaling in ventricles of the late phase of post-infarction HF, highlighting necroptosis itself rather than its linkage with autophagy in LV, and apoptosis in RV. Full article
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Article
Age- and Phenotype-Dependent Changes in Circulating MMP-2 and MMP-9 Activities in Normotensive and Hypertensive Rats
Int. J. Mol. Sci. 2020, 21(19), 7286; https://doi.org/10.3390/ijms21197286 - 02 Oct 2020
Viewed by 719
Abstract
Matrix metalloproteinases (MMPs) are important in the pathogenesis of numerous diseases. The present study aimed to monitor the activation of MMP-2 and MMP-9 in spontaneously hypertensive rats (SHR) and their normotensive counterparts—Wistar-Kyoto rats (WKY). The animals were divided according to age (7, 20, [...] Read more.
Matrix metalloproteinases (MMPs) are important in the pathogenesis of numerous diseases. The present study aimed to monitor the activation of MMP-2 and MMP-9 in spontaneously hypertensive rats (SHR) and their normotensive counterparts—Wistar-Kyoto rats (WKY). The animals were divided according to age (7, 20, and 52 weeks) and phenotype into: WKY-7, WKY-20, WKY-52, SHR-7, SHR-20 and SHR-52 groups. MMP plasma activities were determined by gelatine zymography. We monitored selected parameters of oxidative stress and antioxidant status. N-terminal pro-brain natriuretic peptide (NT-proBNP) was determined as a marker of heart function and neurohumoral activation. SHR-7 showed higher MMP-2 activity compared with WKY-7, while SHR-52 showed lower MMP-2 and MMP-9 activities compared with WKY-52. Examining age-dependent changes in MMP activities, we found a decrease in MMP-2 activity and increase in MMP-9 activity with increasing age in both phenotypes. Parameters of oxidative stress and antioxidant status as well as NT-proBNP levels were not significantly worsened due to aging in SHR. Our results suggest that hypertension is accompanied by varying MMP activation during aging. The results of our study may indicate that MMP-2 inhibition is therapeutically applicable during the development of hypertension, while in developed, stabilized and uncomplicated hypertension, systemic MMP-2 and MMP-9 inhibition may not be desirable. Full article
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Article
Cardioprotective Effect of Novel Matrix Metalloproteinase Inhibitors
Int. J. Mol. Sci. 2020, 21(19), 6990; https://doi.org/10.3390/ijms21196990 - 23 Sep 2020
Cited by 3 | Viewed by 800
Abstract
Background: We recently developed novel matrix metalloproteinase-2 (MMP-2) inhibitor small molecules for cardioprotection against ischemia/reperfusion injury and validated their efficacy in ischemia/reperfusion injury in cardiac myocytes. The aim of the present study was to test our lead compounds for cardioprotection in vivo in [...] Read more.
Background: We recently developed novel matrix metalloproteinase-2 (MMP-2) inhibitor small molecules for cardioprotection against ischemia/reperfusion injury and validated their efficacy in ischemia/reperfusion injury in cardiac myocytes. The aim of the present study was to test our lead compounds for cardioprotection in vivo in a rat model of acute myocardial infarction (AMI) in the presence or absence of hypercholesterolemia, one of the major comorbidities affecting cardioprotection. Methods: Normocholesterolemic adult male Wistar rats were subjected to 30 min of coronary occlusion followed by 120 min of reperfusion to induce AMI. MMP inhibitors (MMPI)-1154 and -1260 at 0.3, 1, and 3 µmol/kg, MMPI-1248 at 1, 3, and 10 µmol/kg were administered at the 25th min of ischemia intravenously. In separate groups, hypercholesterolemia was induced by a 12-week diet (2% cholesterol, 0.25% cholic acid), then the rats were subjected to the same AMI protocol and single doses of the MMPIs that showed the most efficacy in normocholesterolemic animals were tested in the hypercholesterolemic animals. Infarct size/area at risk was assessed at the end of reperfusion in all groups by standard Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining, and myocardial microvascular obstruction (MVO) was determined by thioflavine-S staining. Results: MMPI-1154 at 1 µmol/kg, MMPI-1260 at 3 µmol/kg and ischemic preconditioning (IPC) as the positive control reduced infarct size significantly; however, this effect was not seen in hypercholesterolemic animals. MVO in hypercholesterolemic animals decreased by IPC only. Conclusions: This is the first demonstration that MMPI-1154 and MMPI-1260 showed a dose-dependent infarct size reduction in an in vivo rat AMI model; however, single doses that showed the most efficacy in normocholesterolemic animals were abolished by hypercholesterolemia. The further development of these promising cardioprotective MMPIs should be continued with different dose ranges in the study of hypercholesterolemia and other comorbidities. Full article
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Article
Association between Acrylamide Metabolites and Cardiovascular Risk in Children With Early Stages of Chronic Kidney Disease
Int. J. Mol. Sci. 2020, 21(16), 5855; https://doi.org/10.3390/ijms21165855 - 14 Aug 2020
Cited by 3 | Viewed by 818
Abstract
Cardiovascular disease (CVD) begins early in children with chronic kidney disease (CKD). Reduced nitric oxide (NO) bioavailability has been associated with increased CVD in CKD patients. Children tend to have more exposure to acrylamide, one of the most common toxins in food. We [...] Read more.
Cardiovascular disease (CVD) begins early in children with chronic kidney disease (CKD). Reduced nitric oxide (NO) bioavailability has been associated with increased CVD in CKD patients. Children tend to have more exposure to acrylamide, one of the most common toxins in food. We aimed to determine whether urinary levels of acrylamide metabolites N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-cysteine (GAMA) are associated with CV risk markers in children with CKD. Data on 112 children and adolescents ages three to 18 years old with CKD stage G1–G4 are reported. We observed that 24 h ambulatory blood pressure monitoring (ABPM) abnormalities were greater, and left ventricular (LV) mass and ambulatory arterial stiffness index (AASI) were higher in children with CKD stage G2–G4 versus G1. Patients with CKD stage G2–G4 had a lower urinary acrylamide level, but a higher AAMA-to-GAMA ratio than those with CKD stage G1. Urinary acrylamide level was negatively associated with high systolic blood pressure (SBP) and diastolic BP (DBP) load on 24 h ABPM. Lower urinary levels of acrylamide, AAMA, and GAMA were correlated with LV mass. Additionally, GAMA are superior to AAMA related to NO-related parameters, namely citrulline and symmetric dimethylarginine (SDMA). This study suggests that determinations of urinary acrylamide level and its metabolites in the early stages of pediatric CKD may identify patients at risk of CVD. Further studies should clarify mechanisms underlying acrylamide exposure to define the treatment for protection against CVD. Full article
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Review

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Review
Oxidative Stress, Kinase Activity and Inflammatory Implications in Right Ventricular Hypertrophy and Heart Failure under Hypobaric Hypoxia
Int. J. Mol. Sci. 2020, 21(17), 6421; https://doi.org/10.3390/ijms21176421 - 03 Sep 2020
Cited by 5 | Viewed by 1485
Abstract
High altitude (hypobaric hypoxia) triggers several mechanisms to compensate for the decrease in oxygen bioavailability. One of them is pulmonary artery vasoconstriction and its subsequent pulmonary arterial remodeling. These changes can lead to pulmonary hypertension and the development of right ventricular hypertrophy (RVH), [...] Read more.
High altitude (hypobaric hypoxia) triggers several mechanisms to compensate for the decrease in oxygen bioavailability. One of them is pulmonary artery vasoconstriction and its subsequent pulmonary arterial remodeling. These changes can lead to pulmonary hypertension and the development of right ventricular hypertrophy (RVH), right heart failure (RHF) and, ultimately to death. The aim of this review is to describe the most recent molecular pathways involved in the above conditions under this type of hypobaric hypoxia, including oxidative stress, inflammation, protein kinases activation and fibrosis, and the current therapeutic approaches for these conditions. This review also includes the current knowledge of long-term chronic intermittent hypobaric hypoxia. Furthermore, this review highlights the signaling pathways related to oxidative stress (Nox-derived O2.- and H2O2), protein kinase (ERK5, p38α and PKCα) activation, inflammatory molecules (IL-1β, IL-6, TNF-α and NF-kB) and hypoxia condition (HIF-1α). On the other hand, recent therapeutic approaches have focused on abolishing hypoxia-induced RVH and RHF via attenuation of oxidative stress and inflammatory (IL-1β, MCP-1, SDF-1 and CXCR-4) pathways through phytotherapy and pharmacological trials. Nevertheless, further studies are necessary. Full article
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