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Hypertension and Cardiovascular Diseases: From Etiopathogenesis to Potential Therapeutic Targets

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 29429

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Special Issue Editors

Dr. Iveta Bernatova

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Guest Editor

Centre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia
Interests: experimental hypertension; prehypertension; nitric oxide; social stress; vascular function; aging; iron metabolism; oxidative stress; natural polyphenols
Special Issues, Collections and Topics in MDPI journals

Dr. Monika Bartekova

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Guest Editor

Institute for Heart Research, Centre of Experimental Medicine, Slovak Academy of Sciences, Dúbravská cesta 9, 841 04 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, Collections and Topics in MDPI journals

Dr. Silvia Liskova

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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, Collections and Topics 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 submissions that pass pre-check are 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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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 (12 papers)

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Research

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17 pages, 11523 KiB

Open AccessArticle

Angiotensin System Modulations in Spontaneously Hypertensive Rats and Consequences on Erythrocyte Properties; Action of MLN-4760 and Zofenopril

by Tomas Jasenovec, Dominika Radosinska, Marta Kollarova, Peter Balis, Ezgi Dayar, Iveta Bernatova, Stefan Zorad, Norbert Vrbjar, Sona Cacanyova and Jana Radosinska

Biomedicines 2021, 9(12), 1902; https://doi.org/10.3390/biomedicines9121902 - 14 Dec 2021

Cited by 4 | Viewed by 2183

Abstract

Various pathologies (COVID-19 including) are associated with abnormalities in erythrocyte properties. Hypertension represents an unfavorable condition for erythrocyte quality and is the most prevalent risk factor in COVID-19 patients. ACE2 downregulation that is typical of these patients can further deteriorate cardiovascular health; however, its consequences on erythrocyte properties are not known yet. The aim was to investigate the effect of ACE2 inhibition and the potential beneficial effect of zofenopril on erythrocytes in spontaneously hypertensive rats. ACE2 inhibition induced by MLN-4760 (1 mg/kg/day for 2 weeks) led to deterioration of erythrocyte morphology and osmotic resistance, but plasma markers of oxidative stress, erythrocyte deformability, nitric oxide production and Na,K-ATPase activity were not significantly affected. Zofenopril administration (10 mg/kg/day, initiated after 4-day-lasting ACE2 inhibition) resulted in unexpected increase in angiotensin II plasma levels in both control and ACE-inhibited spontaneously hypertensive rats, but in normalization of osmotic resistance in ACE2-inhibited rats. The overall effect of zofenopril on erythrocyte qualities could be evaluated as beneficial. Full article

(This article belongs to the Special Issue Hypertension and Cardiovascular Diseases: From Etiopathogenesis to Potential Therapeutic Targets)

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18 pages, 4450 KiB

Open AccessArticle

Differences in Distribution and Biological Effects of F₃O₄@PEG Nanoparticles in Normotensive and Hypertensive Rats—Focus on Vascular Function and Liver

by Andrea Micurova, Michal Kluknavsky, Silvia Liskova, Peter Balis, Martin Skratek, Ludmila Okruhlicova, Jan Manka and Iveta Bernatova

Biomedicines 2021, 9(12), 1855; https://doi.org/10.3390/biomedicines9121855 - 07 Dec 2021

Cited by 2 | Viewed by 2119

Abstract

We investigate the distribution and biological effects of polyethylene glycol (PEG)-coated magnetite (Fe₃O₄@PEG) nanoparticles (~30 nm core size, ~51 nm hydrodynamic size, 2 mg Fe/kg/day, intravenously, for two days) in the aorta and liver of Wistar–Kyoto (WKY) and spontaneously hypertensive rats (SHR). Fe₃O₄@PEG had no effect on open-field behaviour but reduced the blood pressure (BP) of Fe₃O₄@PEG-treated SHR (SHRu) significantly, compared to both Fe₃O₄@PEG-treated WKY (WKYu) and saline-treated control SHR (SHRc). The Fe₃O₄@PEG content was significantly elevated in the aorta and liver of SHRu vs. WKYu. Nitric oxide synthase (NOS) activity was unaltered in the aorta, but significantly increased in the liver of SHRu vs. SHRc. In the aorta, Fe₃O₄@PEG treatment increased eNOS, iNOS, NRF2, and DMT1 gene expression (considered main effects). In the liver, Fe₃O₄@PEG significantly elevated eNOS and iNOS gene expression in SHRu vs. SHRc, as well as DMT1 and FTH1 gene expression (considered main effects). Noradrenaline-induced contractions of the femoral arteries were elevated, while endothelium-dependent contractions were reduced in SHRu vs. SHRc. No differences were found in these parameters in WKY rats. In conclusion, the results indicated that the altered haemodynamics in SHR affect the tissue distribution and selected biological effects of Fe₃O₄@PEG in the vasculature and liver, suggesting that caution should be taken when using iron oxide nanoparticles in hypertensive subjects. Full article

(This article belongs to the Special Issue Hypertension and Cardiovascular Diseases: From Etiopathogenesis to Potential Therapeutic Targets)

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18 pages, 1303 KiB

Open AccessArticle

Effects of Renal Denervation on the Enhanced Renal Vascular Responsiveness to Angiotensin II in High-Output Heart Failure: Angiotensin II Receptor Binding Assessment and Functional Studies in Ren-2 Transgenic Hypertensive Rats

by Zuzana Honetschlägerová, Lucie Hejnová, Jiří Novotný, Aleš Marek and Luděk Červenka

Biomedicines 2021, 9(12), 1803; https://doi.org/10.3390/biomedicines9121803 - 30 Nov 2021

Cited by 5 | Viewed by 1511

Abstract

Detailed mechanism(s) of the beneficial effects of renal denervation (RDN) on the course of heart failure (HF) remain unclear. The study aimed to evaluate renal vascular responsiveness to angiotensin II (ANG II) and to characterize ANG II type 1 (AT₁) and type 2 (AT₂) receptors in the kidney of Ren-2 transgenic rats (TGR), a model of ANG II-dependent hypertension. HF was induced by volume overload using aorto-caval fistula (ACF). The studies were performed two weeks after RDN (three weeks after the creation of ACF), i.e., when non-denervated ACF TGR enter the decompensation phase of HF whereas those after RDN are still in the compensation phase. We found that ACF TGR showed lower renal blood flow (RBF) and its exaggerated response to intrarenal ANG II (8 ng); RDN further augmented this responsiveness. We found that all ANG II receptors in the kidney cortex were of the AT₁ subtype. ANG II receptor binding characteristics in the renal cortex did not significantly differ between experimental groups, hence AT₁ alterations are not responsible for renal vascular hyperresponsiveness to ANG II in ACF TGR, denervated or not. In conclusion, maintained renal AT₁ receptor binding combined with elevated ANG II levels and renal vascular hyperresponsiveness to ANG II in ACF TGR influence renal hemodynamics and tubular reabsorption and lead to renal dysfunction in the high-output HF model. Since RDN did not attenuate the RBF decrease and enhanced renal vascular responsiveness to ANG II, the beneficial actions of RDN on HF-related mortality are probably not dominantly mediated by renal mechanism(s). Full article

(This article belongs to the Special Issue Hypertension and Cardiovascular Diseases: From Etiopathogenesis to Potential Therapeutic Targets)

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12 pages, 1740 KiB

Open AccessArticle

The Role of Perivascular Adipose Tissue in Early Changes in Arterial Function during High-Fat Diet and Its Combination with High-Fructose Intake in Rats

by Jozef Torok, Anna Zemancikova, Zuzana Valaskova and Peter Balis

Biomedicines 2021, 9(11), 1552; https://doi.org/10.3390/biomedicines9111552 - 27 Oct 2021

Cited by 3 | Viewed by 1622

Abstract

The aim of the current study was to evaluate the influence of a high-fat diet and its combination with high-fructose intake on young normotensive rats, with focus on the modulatory effect of perivascular adipose tissue (PVAT) on the reactivity of isolated arteries. Six-week-old Wistar–Kyoto rats were treated for 8 weeks with a control diet (10% fat), a high-fat diet (HFD; 45% fat), or a combination of the HFD with a 10% solution of fructose. Contractile and relaxant responses of isolated rat arteries, with preserved and removed PVAT for selected vasoactive stimuli, were recorded isometrically by a force displacement transducer. The results demonstrated that, in young rats, eight weeks of the HFD might lead to body fat accumulation and early excitation of the cardiovascular sympathetic nervous system, as shown by increased heart rate and enhanced arterial contractile responses induced by endogenous noradrenaline released from perivascular sympathetic nerves. The addition of high-fructose intake deteriorated this state by impairment of arterial relaxation and resulted in mild elevation of systolic blood pressure; however, the increase in arterial neurogenic contractions was not detected. The diet-induced alterations in isolated arteries were observed only in the presence of PVAT, indicating that this structure is important in initiation of early vascular changes during the development of metabolic syndrome. Full article

(This article belongs to the Special Issue Hypertension and Cardiovascular Diseases: From Etiopathogenesis to Potential Therapeutic Targets)

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28 pages, 2300 KiB

Open AccessArticle

Effects of Epoxyeicosatrienoic Acid-Enhancing Therapy on the Course of Congestive Heart Failure in Angiotensin II-Dependent Rat Hypertension: From mRNA Analysis towards Functional In Vivo Evaluation

by Petr Kala, Matúš Miklovič, Šárka Jíchová, Petra Škaroupková, Zdeňka Vaňourková, Hana Maxová, Olga Gawrys, Elzbieta Kompanowska-Jezierska, Janusz Sadowski, John D. Imig, John R. Falck, Josef Veselka, Luděk Červenka, Renáta Aiglová, Marek Vícha, Vít Gloger and Miloš Táborský

Biomedicines 2021, 9(8), 1053; https://doi.org/10.3390/biomedicines9081053 - 20 Aug 2021

Cited by 11 | Viewed by 2653

Abstract

This study evaluates the effects of chronic treatment with EET-A, an orally active epoxyeicosatrienoic acid (EETs) analog, on the course of aorto-caval fistula (ACF)-induced heart failure (HF) in Ren-2 transgenic rats (TGR), a model characterized by hypertension and augmented activity of the renin-angiotensin system (RAS). The results were compared with standard pharmacological blockade of the RAS using angiotensin-converting enzyme inhibitor (ACEi). The rationale for employing EET-A as a new treatment approach is based on our findings that apart from increased RAS activity, untreated ACF TGR also shows kidney and left ventricle (LV) tissue deficiency of EETs. Untreated ACF TGR began to die 17 days after creating ACF and were all dead by day 84. The treatment with EET-A alone or ACEi alone improved the survival rate: in 156 days after ACF creation, it was 45.5% and 59.4%, respectively. The combined treatment with EET-A and ACEi appeared to improve the final survival to 71%; however, the difference from either single treatment regimen did not reach significance. Nevertheless, our findings support the notion that targeting the cytochrome P-450-dependent epoxygenase pathway of arachidonic acid metabolism should be considered for the treatment of HF. Full article

(This article belongs to the Special Issue Hypertension and Cardiovascular Diseases: From Etiopathogenesis to Potential Therapeutic Targets)

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19 pages, 2519 KiB

Open AccessArticle

Novel Pharmaceutical Strategy for Selective Abrogation of TSP1-Induced Vascular Dysfunction by Decoy Recombinant CD47 Soluble Receptor in Prophylaxis and Treatment Models

by Molly Yao, Jalicia Sturdivant, Aren Ebrahimi, Samayita Ganguly and Tamer Elbayoumi

Biomedicines 2021, 9(6), 642; https://doi.org/10.3390/biomedicines9060642 - 03 Jun 2021

Cited by 5 | Viewed by 2703

Abstract

Elevated thrombospondin 1 (TSP1) is a prevalent factor, via cognate receptor CD47, in the pathogenesis of cardiovascular conditions, including ischemia-reperfusion injury (IRI) and pulmonary arterial hypertension (PAH). Moreover, TSP1/CD47 interaction has been found to be associated with platelet hyperaggregability and impaired nitric oxide response, exacerbating progression in IRI and PAH. Pathological TSP1 in circulation arises as a target of our novel therapeutic approach. Our “proof-of-concept” pharmacological strategy relies on recombinant human CD47 peptide (rh-CD47p) as a decoy receptor protein (DRP) to specifically bind TSP1 and neutralize TSP1-impaired vasorelaxation, strongly implicated in IRI and PAH. The binding of rh-CD47p and TSP1 was first verified as the primary mechanism via Western blotting and further quantified with modified ELISA, which also revealed a linear molar dose-dependent interaction. Ex vivo, pretreatment protocol with rh-CD47p (rh-CD47p added prior to TSP1 incubation) demonstrated a prophylactic effect against TSP1-impairment of endothelium-dependent vasodilation. Post-treatment set-up (TSP1 incubation prior to rh-CD47p addition), mimicking pre-existing excessive TSP1 in PAH, reversed TSP1-inhibited vasodilation back to control level. Dose titration identified an effective molar dose range (approx. ≥1:3 of tTSP1:rh-CD47p) for prevention of/recovery from TSP1-induced vascular dysfunction. Our results indicate the great potential for proposed novel decoy rh-CD47p-therapy to abrogate TSP1-associated cardiovascular complications, such as PAH. Full article

(This article belongs to the Special Issue Hypertension and Cardiovascular Diseases: From Etiopathogenesis to Potential Therapeutic Targets)

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14 pages, 2194 KiB

Open AccessArticle

Ultra-Small Superparamagnetic Iron-Oxide Nanoparticles Exert Different Effects on Erythrocytes in Normotensive and Hypertensive Rats

by Jana Radosinska, Tomas Jasenovec, Dominika Radosinska, Peter Balis, Angelika Puzserova, Martin Skratek, Jan Manka and Iveta Bernatova

Biomedicines 2021, 9(4), 377; https://doi.org/10.3390/biomedicines9040377 - 02 Apr 2021

Cited by 9 | Viewed by 1965

Abstract

We determined erythrocyte physiological and biochemical properties after the single and repeated administration of ultra-small superparamagnetic iron-oxide nanoparticles (USPIONs) in normotensive Wistar–Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Polyethylene glycol-coated USPIONs (transmission electron microscope detected a mean size of ~30 nm and hydrodynamic size ~51 nm) were intravenously administered to rats either in one infusion at nominal dose 1 mg Fe/kg or in two infusions (administered with a difference of 24 h) at nominal dose 2 mg Fe/kg. Results showed that USPIONs did not deteriorate erythrocyte deformability, nitric oxide production, and osmotic resistance in both experimental settings. Both the single and repeated USPION administration elevated erythrocyte deformability in WKY. However, this effect was not present in SHR; deformability in USPION-treated SHR was significantly lower than in USPION-treated WKY. Nitric oxide production by erythrocytes was increased after a single USPION treatment in WKY, so it can be associated with improvement in erythrocyte deformability. Using biomagnetometry, we revealed significantly lower amounts of USPION-originated iron in erythrocytes in SHR compared with WKY. We found a much faster elimination of USPIONs from erythrocytes in hypertensive rats compared with the normotensive ones, which might be relevant for clinical practice in hypertensive patients undergoing clinical examination with the use of iron-oxide nanoparticles. Full article

(This article belongs to the Special Issue Hypertension and Cardiovascular Diseases: From Etiopathogenesis to Potential Therapeutic Targets)

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16 pages, 12243 KiB

Open AccessArticle

SIRT1 Activation Attenuates the Cardiac Dysfunction Induced by Endothelial Cell-Specific Deletion of CRIF1

by Shuyu Piao, Ikjun Lee, Seon-Ah Jin, Seonhee Kim, Harsha Nagar, Su-jeong Choi, Byeong Hwa Jeon and Cuk-Seong Kim

Biomedicines 2021, 9(1), 52; https://doi.org/10.3390/biomedicines9010052 - 08 Jan 2021

Cited by 10 | Viewed by 2844

Abstract

The CR6-interacting factor1 (CRIF1) mitochondrial protein is indispensable for peptide synthesis and oxidative phosphorylation. Cardiomyocyte-specific deletion of CRIF1 showed impaired mitochondrial function and cardiomyopathy. We developed an endothelial cell-specific CRIF1 deletion mouse to ascertain whether dysfunctional endothelial CRIF1 influences cardiac function and is mediated by the antioxidant protein sirtuin 1 (SIRT1). We also examined the effect of the potent SIRT1 activator SRT1720 on cardiac dysfunction. Mice with endothelial cell-specific CRIF1 deletion showed an increased heart-to-body weight ratio, increased lethality, and markedly reduced fractional shortening of the left ventricle, resulting in severe cardiac dysfunction. Moreover, endothelial cell-specific CRIF1 deletion resulted in mitochondrial dysfunction, reduced ATP levels, inflammation, and excessive oxidative stress in heart tissues, associated with decreased SIRT1 expression. Intraperitoneal injection of SRT1720 ameliorated cardiac dysfunction by activating endothelial nitric oxide synthase, reducing oxidative stress, and inhibiting inflammation. Furthermore, the decreased endothelial junction-associated protein zonula occludens-1 in CRIF1-deleted mice was significantly recovered after SRT1720 treatment. Our results suggest that endothelial CRIF1 plays an important role in maintaining cardiac function, and that SIRT1 induction could be a therapeutic strategy for endothelial dysfunction-induced cardiac dysfunction. Full article

(This article belongs to the Special Issue Hypertension and Cardiovascular Diseases: From Etiopathogenesis to Potential Therapeutic Targets)

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15 pages, 1615 KiB

Open AccessArticle

Apple Supplementation Improves Hemodynamic Parameter and Attenuates Atherosclerosis in High-Fat Diet-Fed Apolipoprotein E-Knockout Mice

by Raffaella Soleti, Charlotte Trenteseaux, Lionel Fizanne, Marine Coué, Gregory Hilairet, Fatima Kasbi-Chadli, Patricia Mallegol, Julien Chaigneau, Jerome Boursier, Michel Krempf, Mathilde Orsel, Khadija Ouguerram and Ramaroson Andriantsitohaina

Biomedicines 2020, 8(11), 495; https://doi.org/10.3390/biomedicines8110495 - 12 Nov 2020

Cited by 2 | Viewed by 1920

Abstract

Epidemiological studies describe the association between apple consumption and improved cardiovascular and metabolic dysfunction. Our recent multiparametric screening on cellular model studies has shown that apples exhibit vascular tropism including Granny Smith (GS) variety independently of the storage condition. The present study aimed to evaluate the cardiovascular and metabolic protection of supplementation of GS variety after storage in classic cold (GSCC) and extreme ultra-low oxygen conditions (GSXO) in the apolipoprotein E-deficient 8-week-old mice fed with high fat diet for 14 weeks. Supplementation with GSCC and GXO decreases circulating triglycerides, the expression of genes involved in lipogenesis, without change in cholesterol and glucose concentrations and HOMA-IR. Only GSXO supplementation ameliorates body weight gain, insulin level, and HDL/LDL ratio. GSXO supplementation does not modify cardiac parameters; while supplementation with GSCC decreases heart rate and improves cardiac output. Interestingly, GSCC and GSXO reduce systolic and diastolic blood pressure with a differential time course of action. These effects are associated with substantial decrease of atherosclerotic lesions. These data reinforce the knowledge about the vascular tropism of apple supplementation and underscore their ability to improve both cardiovascular and metabolic alterations in a mouse model of atherosclerosis. Full article

(This article belongs to the Special Issue Hypertension and Cardiovascular Diseases: From Etiopathogenesis to Potential Therapeutic Targets)

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18 pages, 1555 KiB

Open AccessArticle

Fetal Undernutrition Induces Resistance Artery Remodeling and Stiffness in Male and Female Rats Independent of Hypertension

by Perla Y. Gutiérrez-Arzapalo, Pilar Rodríguez-Rodríguez, David Ramiro-Cortijo, Marta Gil-Ortega, Beatriz Somoza, Ángel Luis López de Pablo, Maria del Carmen González and Silvia M. Arribas

Biomedicines 2020, 8(10), 424; https://doi.org/10.3390/biomedicines8100424 - 16 Oct 2020

Cited by 7 | Viewed by 2362

Abstract

Fetal undernutrition programs hypertension and cardiovascular diseases, and resistance artery remodeling may be a contributing factor. We aimed to assess if fetal undernutrition induces resistance artery remodeling and the relationship with hypertension. Sprague–Dawley dams were fed ad libitum (Control) or with 50% of control intake between days 11 and 21 of gestation (maternal undernutrition, MUN). In six-month-old male and female offspring we assessed blood pressure (anesthetized and tail-cuff); mesenteric resistance artery (MRA) structure and mechanics (pressure myography), cellular and internal elastic lamina (IEL) organization (confocal microscopy) and plasma MMP-2 and MMP-9 activity (zymography). Systolic blood pressure (SBP, tail-cuff) and plasma MMP activity were assessed in 18-month-old rats. At the age of six months MUN males exhibited significantly higher blood pressure (anesthetized or tail-cuff) and plasma MMP-9 activity, while MUN females did not exhibit significant differences, compared to sex-matched controls. MRA from 6-month-old MUN males and females showed a smaller diameter, reduced adventitial, smooth muscle cell density and IEL fenestra area, and a leftward shift of stress-strain curves. At the age of eighteen months SBP and MMP-9 activity were higher in both MUN males and females, compared to sex-matched controls. These data suggest that fetal undernutrition induces MRA inward eutrophic remodeling and stiffness in both sexes, independent of blood pressure level. Resistance artery structural and mechanical alterations can participate in the development of hypertension in aged females and may contribute to adverse cardiovascular events associated with low birth weight in both sexes. Full article

(This article belongs to the Special Issue Hypertension and Cardiovascular Diseases: From Etiopathogenesis to Potential Therapeutic Targets)

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12 pages, 261 KiB

Open AccessArticle

Non-Adherence to Statin Treatment in Older Patients with Peripheral Arterial Disease Depending on Persistence Status

by Martin Wawruch, Gejza Wimmer, Jr., Jan Murin, Martina Paduchova, Miriam Petrova, Tomas Tesar, Petra Matalova, Beata Havelkova, Michal Trnka and Emma Aarnio

Biomedicines 2020, 8(10), 378; https://doi.org/10.3390/biomedicines8100378 - 25 Sep 2020

Cited by 2 | Viewed by 1861

Abstract

The effectiveness of statins in secondary prevention of peripheral arterial disease (PAD) largely depends on patients’ adherence to treatment. The aims of our study were: (a) to analyze non-adherence during the whole follow-up in persistent patients, and only during persistence for non-persistent patients; (b) to identify factors associated with non-adherence separately among persistent and non-persistent patients. A cohort of 8330 statin users aged ≥65 years, in whom PAD was newly diagnosed between January 2012–December 2012, included 5353 patients persistent with statin treatment, and 2977 subjects who became non-persistent during the 5-year follow-up. Non-adherence was defined using the proportion of days covered <80%. Patient- and statin-related characteristics associated with non-adherence were identified with binary logistic regression. A significantly higher proportion of non-adherent patients was found among non-persistent patients compared to persistent subjects (43.6% vs. 29.6%; p < 0.001). Associated with non-adherence in both persistent and non-persistent patients was high intensity statin treatment, while in non-persistent patients, it was employment and increasing number of medications. In patients with a poor adherence during their persistent period, an increased risk for discontinuation may be expected. However, there is also non-adherence among persistent patients. There are differences in factors associated with non-adherence depending on patients’ persistence. Full article

(This article belongs to the Special Issue Hypertension and Cardiovascular Diseases: From Etiopathogenesis to Potential Therapeutic Targets)

Review

Jump to: Research

19 pages, 543 KiB

Open AccessReview

Advances in Cardiovascular Biomarker Discovery

by Crystal M. Ghantous, Layla Kamareddine, Rima Farhat, Fouad A. Zouein, Stefania Mondello, Firas Kobeissy and Asad Zeidan

Biomedicines 2020, 8(12), 552; https://doi.org/10.3390/biomedicines8120552 - 30 Nov 2020

Cited by 35 | Viewed by 4208

Abstract

Cardiovascular diseases are the leading causes of mortality worldwide. Among them, hypertension and its pathological complications pose a major risk for the development of other cardiovascular diseases, including heart failure and stroke. Identifying novel and early stage biomarkers of hypertension and other cardiovascular diseases is of paramount importance in predicting and preventing the major morbidity and mortality associated with these diseases. Biomarkers of such diseases or predisposition to their development are identified by changes in a specific indicator’s expression between healthy individuals and patients. These include changes in protein and microRNA (miRNA) levels. Protein profiling using mass spectrometry and miRNA screening utilizing microarray and sequencing have facilitated the discovery of proteins and miRNA as biomarker candidates. In this review, we summarized some of the different, promising early stage protein and miRNA biomarker candidates as well as the currently used biomarkers for hypertension and other cardiovascular diseases. Although a number of promising markers have been identified, it is unlikely that a single biomarker will unambiguously aid in the classification of these diseases. A multi-marker panel-strategy appears useful and promising for classifying and refining risk stratification among patients with cardiovascular disease. Full article

(This article belongs to the Special Issue Hypertension and Cardiovascular Diseases: From Etiopathogenesis to Potential Therapeutic Targets)

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