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Role of Ion Channels in Cardiovascular and Other Human Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (20 September 2023) | Viewed by 7632

Special Issue Editors

Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary
Interests: TRPV pharmacology; cardiovascular diseases; diabetes
Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, 22 Móricz Zsigmond Street, 4032 Debrecen, Hungary
Interests: TRP channels, myocardial contractility; vascular biology; clinical biomarkers in cardiovascular diseases; angiotensin converting enzymes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore, presenting in the membranes of all cells. The predecessors focused their attention on establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. In recent years, the discoveries of the role of ion channels have uncovered their critical role in vascular disease and other human diseases.

This Special Issue will provide the latest progress in, and current understanding of, the contribution of ion channels in multiple aspects of human diseases, especially vascular disease. The scope of this Special Issue will be dedicated to the impact of ion channels and transporters in diseases, including but not limited to cell biology, pharmacology, pharmacogenetics, drug resistance, treatment efficacy and toxicity, drug development, cell microenvironment, the targeting of ion channels, and disease resistance to therapy. We warmly welcome submissions, including original research papers and reviews, on these widely discussed topics.

Dr. Róbert Pórszász
Prof. Dr. Attila Tóth
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. 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

  • ion channel
  • signal transduction
  • endothelial cell
  • vascular smooth muscle
  • vascular remodeling
  • vascular tone
  • microcirculation
  • vascular regeneration
  • neuronal disorders
  • kidney disorders
  • eye disorders
  • channelopathy

Published Papers (5 papers)

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Research

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15 pages, 4167 KiB  
Article
Multiple-Factors-Induced Rheumatoid Arthritis Synoviocyte Activation Is Attenuated by the α2-Adrenergic Receptor Agonist Dexmedetomidine
by Dongun Lee and Jeong Hee Hong
Int. J. Mol. Sci. 2023, 24(13), 10756; https://doi.org/10.3390/ijms241310756 - 28 Jun 2023
Viewed by 855
Abstract
Dexmedetomidine (Dex) has analgesic and sedative properties and anti-inflammatory functions. Although the effects of Dex on arthritis have been revealed, the physiological mechanism underlying the interaction between Dex and rheumatoid arthritis (RA)-mediated inflammatory cytokines has not been fully studied. Inflamed and migrated fibroblast-like [...] Read more.
Dexmedetomidine (Dex) has analgesic and sedative properties and anti-inflammatory functions. Although the effects of Dex on arthritis have been revealed, the physiological mechanism underlying the interaction between Dex and rheumatoid arthritis (RA)-mediated inflammatory cytokines has not been fully studied. Inflamed and migrated fibroblast-like synoviocytes (FLSs) are involved in RA severity. Thus, we aimed to determine the effects of Dex on RA-FLSs treated with inflammatory cytokines and a growth factor as multiple stimulating inputs. TNF-α, IL-6, and EGF as multiple stimulating inputs increased the cAMP concentration of RA-FLSs, while Dex treatment reduced cAMP concentration. Dex reduced electroneutral sodium-bicarbonate cotransporter 1 (NBCn1) expression, NBC activity, and subsequent RA-FLS migration. The mRNA expression levels of RA-related factors, such as inflammatory cytokines and osteoclastogenesis factors, were enhanced by multiple-input treatment. Notably, Dex effectively reduced these expression levels in RA-FLSs. These results indicate that multiple inflammatory or stimulating inputs enhance RA-FLS migration, and treatment with Dex relieves activated RA-FLSs, suggesting that Dex is a potential therapeutic drug for RA. Full article
(This article belongs to the Special Issue Role of Ion Channels in Cardiovascular and Other Human Diseases)
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21 pages, 3646 KiB  
Article
TRPA1 as Target in Myocardial Infarction
by Clara Hoebart, Attila Kiss, Patrick M. Pilz, Petra L. Szabo, Bruno K. Podesser, Michael J. M. Fischer and Stefan Heber
Int. J. Mol. Sci. 2023, 24(3), 2516; https://doi.org/10.3390/ijms24032516 - 28 Jan 2023
Cited by 1 | Viewed by 1396
Abstract
Transient receptor potential cation channel subfamily A member 1 (TRPA1), an ion channel primarily expressed on sensory neurons, can be activated by substances occurring during myocardial infarction. Aims were to investigate whether activation, inhibition, or absence of TRPA1 affects infarcts and to explore [...] Read more.
Transient receptor potential cation channel subfamily A member 1 (TRPA1), an ion channel primarily expressed on sensory neurons, can be activated by substances occurring during myocardial infarction. Aims were to investigate whether activation, inhibition, or absence of TRPA1 affects infarcts and to explore underlying mechanisms. In the context of myocardial infarction, rats received a TRPA1 agonist, an antagonist, or vehicle at different time points, and infarct size was assessed. Wild type and TRPA1 knockout mice were also compared in this regard. In vitro, sensory neurons were co-cultured with cardiomyocytes and subjected to a model of ischemia-reperfusion. Although there was a difference between TRPA1 activation or inhibition in vivo, no experimental group was different to control animals in infarct size, which also applies to animals lacking TRPA1. In vitro, survival probability of cardiomyocytes challenged by ischemia-reperfusion increased from 32.8% in absence to 45.1% in presence of sensory neurons, which depends, at least partly, on TRPA1. This study raises doubts about whether TRPA1 is a promising target to reduce myocardial damage within a 24 h period. The results are incompatible with relevant enlargements of infarcts by TRPA1 activation or inhibition, which argues against adverse effects when TRPA1 is targeted for other indications. Full article
(This article belongs to the Special Issue Role of Ion Channels in Cardiovascular and Other Human Diseases)
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11 pages, 990 KiB  
Article
Impact of the TRPV2 Inhibitor on Advanced Heart Failure in Patients with Muscular Dystrophy: Exploratory Study of Biomarkers Related to the Efficacy of Tranilast
by Chisato Takahashi, Mariko Oishi, Yuko Iwata, Keiko Maekawa and Tsuyoshi Matsumura
Int. J. Mol. Sci. 2023, 24(3), 2167; https://doi.org/10.3390/ijms24032167 - 21 Jan 2023
Viewed by 1343
Abstract
Cardiomyopathy is the leading cause of death in patients with muscular dystrophy (MD). Tranilast, a widely used anti-allergic drug, has displayed inhibitory activity against the transient receptor potential cation channel subfamily V member 2 and improved cardiac function in MD patients. To identify [...] Read more.
Cardiomyopathy is the leading cause of death in patients with muscular dystrophy (MD). Tranilast, a widely used anti-allergic drug, has displayed inhibitory activity against the transient receptor potential cation channel subfamily V member 2 and improved cardiac function in MD patients. To identify urinary biomarkers that assess improved cardiac function after tranilast administration, we performed a urinary metabolomic study focused on oxidative fatty acids. Accompanying the clinical trial of tranilast, urine specimens were collected over 24 weeks from MD patients with advanced heart failure. Urinary levels of tetranor-PGDM (tetranor-prostaglandin D metabolite), a metabolite of prostaglandin D2, significantly decreased 12 weeks after tranilast administration and were correlated with BNP. These results suggest that prostaglandin-mediated inflammation, which increases with the pathological progression of heart failure in MD patients, was attenuated. Urinary prostaglandin E3 (PGE3) levels significantly increased 4 weeks after tranilast administration. There were positive correlations between the urinary levels of PGE3 and 8-hydroxy-2′-deoxyguanosine, an oxidative stress marker. High PGE3 levels may have a protective effect against cardiomyopathy in MD patients with high oxidative stress. Although further validation studies are necessary, urinary tetranor-PGDM and PGE3 levels may help the current understanding of the extent of advanced heart failure in patients with MD after tranilast administration. Full article
(This article belongs to the Special Issue Role of Ion Channels in Cardiovascular and Other Human Diseases)
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Review

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17 pages, 695 KiB  
Review
The Vanilloid (Capsaicin) Receptor TRPV1 in Blood Pressure Regulation: A Novel Therapeutic Target in Hypertension?
by Arpad Szallasi
Int. J. Mol. Sci. 2023, 24(10), 8769; https://doi.org/10.3390/ijms24108769 - 15 May 2023
Viewed by 1608
Abstract
Today’s sedentary lifestyle with excess food and little exercise increases the number of people with hypertension, a major risk factor for stroke. New knowledge of treatments in this field is of utmost importance. In animal experiments, the activation by capsaicin of TRPV1-expressing sensory [...] Read more.
Today’s sedentary lifestyle with excess food and little exercise increases the number of people with hypertension, a major risk factor for stroke. New knowledge of treatments in this field is of utmost importance. In animal experiments, the activation by capsaicin of TRPV1-expressing sensory afferents evokes a drop in blood pressure by triggering the Bezold–Jarisch reflex. In hypertensive rats, capsaicin reduces blood pressure. Conversely, genetic ablation of the TRPV1 receptor results in elevated nocturnal (but not diurnal) blood pressure. These observations imply a therapeutic potential for TRPV1 activation in hypertensive patients. Indeed, in a major epidemiological study involving 9273 volunteers, dietary capsaicin was found to lower the risk for hypertension. New research indicates that the mechanism of action of capsaicin on blood pressure regulation is far more complex than previously thought. In addition to the well-recognized role of capsaicin-sensitive afferents in blood pressure regulation, TRPV1 seems to be expressed both in endothelial cells and vascular smooth muscle. This review aims to evaluate the therapeutic potential of TRPV1-targeting drugs in hypertensive patients. Full article
(This article belongs to the Special Issue Role of Ion Channels in Cardiovascular and Other Human Diseases)
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21 pages, 3519 KiB  
Review
Automated Patch-Clamp and Induced Pluripotent Stem Cell-Derived Cardiomyocytes: A Synergistic Approach in the Study of Brugada Syndrome
by Dario Melgari, Serena Calamaio, Anthony Frosio, Rachele Prevostini, Luigi Anastasia, Carlo Pappone and Ilaria Rivolta
Int. J. Mol. Sci. 2023, 24(7), 6687; https://doi.org/10.3390/ijms24076687 - 03 Apr 2023
Cited by 2 | Viewed by 1725
Abstract
The development of high-throughput automated patch-clamp technology is a recent breakthrough in the field of Brugada syndrome research. Brugada syndrome is a heart disorder marked by abnormal electrocardiographic readings and an elevated risk of sudden cardiac death due to arrhythmias. Various experimental models, [...] Read more.
The development of high-throughput automated patch-clamp technology is a recent breakthrough in the field of Brugada syndrome research. Brugada syndrome is a heart disorder marked by abnormal electrocardiographic readings and an elevated risk of sudden cardiac death due to arrhythmias. Various experimental models, developed either in animals, cell lines, human tissue or computational simulation, play a crucial role in advancing our understanding of this condition, and developing effective treatments. In the perspective of the pathophysiological role of ion channels and their pharmacology, automated patch-clamp involves a robotic system that enables the simultaneous recording of electrical activity from multiple single cells at once, greatly improving the speed and efficiency of data collection. By combining this approach with the use of patient-derived cardiomyocytes, researchers are gaining a more comprehensive view of the underlying mechanisms of heart disease. This has led to the development of more effective treatments for those affected by cardiovascular conditions. Full article
(This article belongs to the Special Issue Role of Ion Channels in Cardiovascular and Other Human Diseases)
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