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Cardiology and Vascular Health: From Molecular Mechanisms to Therapies

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

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 11133

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Special Issue Editor

Prof. Dr. Simon Rabkin

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Guest Editor

Division of Cardiology, University of British Columbia, 9th Floor 2775 Laurel St., Vancouver, BC V5Z 1M9, Canada
Interests: cardiac electrophysiology; heart arrhythmia; atrial fibrillation; heart failure; palpitations; myocarditis; neurocardiology; machine learning
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Special Issue Information

Dear Colleagues,

Attaining cardiovascular health involves understanding the cellular, molecular, ionic pathways and their genetics involved in the induction and treatment of cardiovascular diseases. The enormous numbers of factors involved in the process leading to cardiovascular disease sometimes exceed the capacity of the mind to integrate them in a meaning way. The use of computer algorithms (machine learning) holds the promise identifying patterns that may not be readily apparent. Conditions such as atherosclerosis, heart failure, cardiomyopathy, coronary artery disease, cardiac arrhythmias, valvular heart disease, as well as diseases of the aorta and small vessels remain challenges for cardiovascular medicine. Pharmacologic therapy is based on understanding the fundamental basis of the disease whether it is a cardiac ion channel disorder, a receptor defect or another kind of disorder.

The aims of this Special issue of IJMS are several fold. It aims to create an understanding of the best machine learning approaches to unravel basic molecular, cellular genetic and other mechanism and pathways leading to the different kinds of cardiovascular disease. It also aims to synthesize the approaches whereby machine learning technology can lead to interventions or drug discovery that can treat or prevent cardiovascular diseases leading to improved cardiovascular health.

Pure clinical studies are out of scope of this Special Issue, however, clinical submissions with biomolecular experiments are welcome.

Prof. Dr. Simon W. Rabkin
Guest Editor

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

Machine learning
cardiovascular molecular biology
signal transduction
genetics
ion channels
drug discovery
arrhythmias
heart failure
aortic diseases
Valvular heart disease
Atherosclerosis

Published Papers (4 papers)

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Research

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15 pages, 3512 KiB

Open AccessArticle

Targeting Fatty Acid-Binding Protein 4 Improves Pathologic Features of Aortic Stenosis

by Mattie Garaikoetxea, Ernesto Martín-Núñez, Adela Navarro, Lara Matilla, Amaya Fernández-Celis, Vanessa Arrieta, Amaia García-Peña, Alicia Gainza, Virginia Álvarez, Rafael Sádaba, Eva Jover and Natalia López-Andrés

Int. J. Mol. Sci. 2022, 23(15), 8439; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158439 - 29 Jul 2022

Cited by 5 | Viewed by 1971

Abstract

Aortic stenosis (AS) is a fibrocalcific disease of the aortic valves (AVs). Sex-differences in AS pathophysiology have recently been described. High levels of fatty acid-binding protein 4 (FAPB4) in atherosclerotic plaques have been associated with increased local inflammation, endothelial dysfunction, and plaque vulnerability. FABP4 pharmacological blockade has been shown to be effective for the treatment of atherosclerosis by modulating metabolic and inflammatory pathways. We aimed to analyze the sex-specific expression of FABP4 in AS and its potential role as a therapeutic target. A total of 226 patients (61.5% men) with severe AS undergoing surgical AV replacement were recruited. The FABP4 levels were increased in the AVs of AS patients compared to the control subjects, showing greater expression in the fibrocalcific regions. Male AVs exhibited higher levels of FABP4 compared to females, correlating with markers of inflammation (IL-6, Rantes), apoptosis (Bax, caspase-3, Bcl-2), and calcification (IL-8, BMP-2 and BMP-4). VICs derived from AS patients showed the basal expression of FABP4 in vitro. Osteogenic media induced upregulation of intracellular and secreted FABP4 levels in male VICs after 7 days, along with increased levels of inflammatory, pro-apoptotic, and osteogenic markers. Treatment with BMS309403, a specific inhibitor of FABP4, prevented from all of these changes. Thus, we propose FABP4 as a new sex-specific pharmacological therapeutic target in AS. Full article

(This article belongs to the Special Issue Cardiology and Vascular Health: From Molecular Mechanisms to Therapies)

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14 pages, 2995 KiB

Open AccessArticle

Disruption of a Conservative Motif in the C-Terminal Loop of the KCNQ1 Channel Causes LQT Syndrome

by Maria Karlova, Denis V. Abramochkin, Ksenia B. Pustovit, Tatiana Nesterova, Valery Novoseletsky, Gildas Loussouarn, Elena Zaklyazminskaya and Olga S. Sokolova

Int. J. Mol. Sci. 2022, 23(14), 7953; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23147953 - 19 Jul 2022

Cited by 1 | Viewed by 1897

Abstract

We identified a single nucleotide variation (SNV) (c.1264A > G) in the KCNQ1 gene in a 5-year-old boy who presented with a prolonged QT interval. His elder brother and mother, but not sister and father, also had this mutation. This missense mutation leads to a p.Lys422Glu (K422E) substitution in the Kv7.1 protein that has never been mentioned before. We inserted this substitution in an expression plasmid containing Kv7.1 cDNA and studied the electrophysiological characteristics of the mutated channel expressed in CHO-K1, using the whole-cell configuration of the patch-clamp technique. Expression of the mutant Kv7.1 channel in both homo- and heterozygous conditions in the presence of auxiliary subunit KCNE1 results in a significant decrease in tail current densities compared to the expression of wild-type (WT) Kv7.1 and KCNE1. This study also indicates that K422E point mutation causes a dominant negative effect. The mutation was not associated with a trafficking defect; the mutant channel protein was confirmed to localize at the cell membrane. This mutation disrupts the poly-Lys strip in the proximal part of the highly conserved cytoplasmic A–B linker of Kv7.1 that was not shown before to be crucial for channel functioning. Full article

(This article belongs to the Special Issue Cardiology and Vascular Health: From Molecular Mechanisms to Therapies)

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15 pages, 4372 KiB

Open AccessArticle

Convolutional Neural Networks for Mechanistic Driver Detection in Atrial Fibrillation

by Gonzalo Ricardo Ríos-Muñoz, Francisco Fernández-Avilés and Ángel Arenal

Int. J. Mol. Sci. 2022, 23(8), 4216; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084216 - 11 Apr 2022

Cited by 6 | Viewed by 2223

Abstract

The maintaining and initiating mechanisms of atrial fibrillation (AF) remain controversial. Deep learning is emerging as a powerful tool to better understand AF and improve its treatment, which remains suboptimal. This paper aims to provide a solution to automatically identify rotational activity drivers in endocardial electrograms (EGMs) with convolutional recurrent neural networks (CRNNs). The CRNN model was compared with two other state-of-the-art methods (SimpleCNN and attention-based time-incremental convolutional neural network (ATI-CNN)) for different input signals (unipolar EGMs, bipolar EGMs, and unipolar local activation times), sampling frequencies, and signal lengths. The proposed CRNN obtained a detection score based on the Matthews correlation coefficient of 0.680, an ATI-CNN score of 0.401, and a SimpleCNN score of 0.118, with bipolar EGMs as input signals exhibiting better overall performance. In terms of signal length and sampling frequency, no significant differences were found. The proposed architecture opens the way for new ablation strategies and driver detection methods to better understand the AF problem and its treatment. Full article

(This article belongs to the Special Issue Cardiology and Vascular Health: From Molecular Mechanisms to Therapies)

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Review

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60 pages, 2211 KiB

Open AccessReview

Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review

by Federica Conte, Juda-El Sam, Dirk J. Lefeber and Robert Passier

Int. J. Mol. Sci. 2023, 24(10), 8632; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24108632 - 11 May 2023

Cited by 3 | Viewed by 4251

Abstract

Heart failure (HF) is a progressive chronic disease that remains a primary cause of death worldwide, affecting over 64 million patients. HF can be caused by cardiomyopathies and congenital cardiac defects with monogenic etiology. The number of genes and monogenic disorders linked to development of cardiac defects is constantly growing and includes inherited metabolic disorders (IMDs). Several IMDs affecting various metabolic pathways have been reported presenting cardiomyopathies and cardiac defects. Considering the pivotal role of sugar metabolism in cardiac tissue, including energy production, nucleic acid synthesis and glycosylation, it is not surprising that an increasing number of IMDs linked to carbohydrate metabolism are described with cardiac manifestations. In this systematic review, we offer a comprehensive overview of IMDs linked to carbohydrate metabolism presenting that present with cardiomyopathies, arrhythmogenic disorders and/or structural cardiac defects. We identified 58 IMDs presenting with cardiac complications: 3 defects of sugar/sugar-linked transporters (GLUT3, GLUT10, THTR1); 2 disorders of the pentose phosphate pathway (G6PDH, TALDO); 9 diseases of glycogen metabolism (GAA, GBE1, GDE, GYG1, GYS1, LAMP2, RBCK1, PRKAG2, G6PT1); 29 congenital disorders of glycosylation (ALG3, ALG6, ALG9, ALG12, ATP6V1A, ATP6V1E1, B3GALTL, B3GAT3, COG1, COG7, DOLK, DPM3, FKRP, FKTN, GMPPB, MPDU1, NPL, PGM1, PIGA, PIGL, PIGN, PIGO, PIGT, PIGV, PMM2, POMT1, POMT2, SRD5A3, XYLT2); 15 carbohydrate-linked lysosomal storage diseases (CTSA, GBA1, GLA, GLB1, HEXB, IDUA, IDS, SGSH, NAGLU, HGSNAT, GNS, GALNS, ARSB, GUSB, ARSK). With this systematic review we aim to raise awareness about the cardiac presentations in carbohydrate-linked IMDs and draw attention to carbohydrate-linked pathogenic mechanisms that may underlie cardiac complications. Full article

(This article belongs to the Special Issue Cardiology and Vascular Health: From Molecular Mechanisms to Therapies)

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