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

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).

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
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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. 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 2000 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 (8 papers)

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Research

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Article
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
Biomedicines 2021, 9(8), 1053; https://doi.org/10.3390/biomedicines9081053 - 20 Aug 2021
Viewed by 388
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 [...] Read more.
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
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Article
Novel Pharmaceutical Strategy for Selective Abrogation of TSP1-Induced Vascular Dysfunction by Decoy Recombinant CD47 Soluble Receptor in Prophylaxis and Treatment Models
Biomedicines 2021, 9(6), 642; https://doi.org/10.3390/biomedicines9060642 - 03 Jun 2021
Cited by 2 | Viewed by 764
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 [...] Read more.
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
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Article
Ultra-Small Superparamagnetic Iron-Oxide Nanoparticles Exert Different Effects on Erythrocytes in Normotensive and Hypertensive Rats
Biomedicines 2021, 9(4), 377; https://doi.org/10.3390/biomedicines9040377 - 02 Apr 2021
Cited by 1 | Viewed by 619
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 [...] Read more.
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
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Article
SIRT1 Activation Attenuates the Cardiac Dysfunction Induced by Endothelial Cell-Specific Deletion of CRIF1
Biomedicines 2021, 9(1), 52; https://doi.org/10.3390/biomedicines9010052 - 08 Jan 2021
Viewed by 844
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 [...] Read more.
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
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Article
Apple Supplementation Improves Hemodynamic Parameter and Attenuates Atherosclerosis in High-Fat Diet-Fed Apolipoprotein E-Knockout Mice
Biomedicines 2020, 8(11), 495; https://doi.org/10.3390/biomedicines8110495 - 12 Nov 2020
Viewed by 639
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 [...] Read more.
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
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Article
Fetal Undernutrition Induces Resistance Artery Remodeling and Stiffness in Male and Female Rats Independent of Hypertension
Biomedicines 2020, 8(10), 424; https://doi.org/10.3390/biomedicines8100424 - 16 Oct 2020
Cited by 1 | Viewed by 844
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 [...] Read more.
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
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Article
Non-Adherence to Statin Treatment in Older Patients with Peripheral Arterial Disease Depending on Persistence Status
Biomedicines 2020, 8(10), 378; https://doi.org/10.3390/biomedicines8100378 - 25 Sep 2020
Viewed by 693
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; [...] Read more.
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

Review

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Review
Advances in Cardiovascular Biomarker Discovery
Biomedicines 2020, 8(12), 552; https://doi.org/10.3390/biomedicines8120552 - 30 Nov 2020
Cited by 3 | Viewed by 1117
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 [...] Read more.
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
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