Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Cardiac Diseases: Molecular Pathology, Diagnostics, and Therapeutics

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

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 (20 June 2023) | Viewed by 10271

Share This Special Issue

Special Issue Editor

Dr. Chin-Feng Tsai

E-Mail Website
Guest Editor

School of Medicine, Chung Shan Medical University Division of Cardiology, Chung Shan Medical University Hospital, Taichung City, Taiwan
Interests: arrhythmia; electrophysiology; ablation and device therapy; cardiac fibrosis; signal pathway; atherosclerosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite the progress in pharmacotherapy, interventional cardiology and surgery, cardiovascular diseases remain the leading cause of death worldwide. Due to the complexity of the etiology and the clinical manifestation, the diagnosis and treatment of complex cardiovascular disease are still unmet medical needs. Moreover, the molecular and cellular mechanisms underlying various cardiovascular diseases are not completely understood. Therefore, understanding the mechanisms underlying the pathogenesis of various cardiovascular disorders will confer a great opportunity to delineate diagnostic tools and therapeutic interventions for early detection and effective therapy of the cardiovascular diseases.

This Special Issue will focus on advanced research on cardiac diseases that may provide solutions to the challenges of diagnosing and treating patients with cardiovascular diseases. We are looking for original research articles, communications, and comprehensive reviews. Articles that investigate novel molecular mechanisms from the perspective of diagnosis/therapy are especially welcomed.

Dr. Chin-Feng Tsai
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

cardiovascular disease
atherosclerosis
arrhythmia
heart failure
signal pathway
molecular/cellular mechanism
pathogenesis

Published Papers (5 papers)

Download All Papers

Research

Jump to: Review

24 pages, 21173 KiB

Open AccessArticle

The Regulatory Effect of Receptor-Interacting Protein Kinase 3 on CaMKIIδ in TAC-Induced Myocardial Hypertrophy

by Jianan Qian, Jingjing Zhang, Ji Cao, Xue Wang, Wei Zhang and Xiangfan Chen

Int. J. Mol. Sci. 2023, 24(19), 14529; https://doi.org/10.3390/ijms241914529 - 26 Sep 2023

Viewed by 893

Abstract

Necroptosis is a newly discovered mechanism of cell death, and its key regulatory role is attributed to the interaction of receptor-interacting protein kinases (RIPKs) RIPK1 and RIPK3. Ca²⁺/calmodulin-dependent protein kinase (CaMKII) is a newly discovered RIPK3 substrate, and its alternative splicing plays a fundamental role in cardiovascular diseases. In the present study, we aimed to explore the role and mechanism of necroptosis and alternative splicing of CaMKIIδ in myocardial hypertrophy. Transverse aortic constriction (TAC) was performed on wild-type and knockout mice to establish the model of myocardial hypertrophy. After 3 weeks, echocardiography, cardiac index, cross-sectional area of myocardial cells, hypertrophic gene expression, myocardial damage, and fibers were assessed. Moreover, we detected the levels of inflammatory factors (IL-6 and TNF-α) and examined the expressions of necroptosis-related proteins RIPK3, RIPK1, and phosphorylated MLKL. Meanwhile, we tested the expression levels of splicing factors ASF/SF2 and SC-35 in an attempt to explore CaMKII δ. The relationship between variable splicing disorder and the expression levels of splicing factors ASF/SF2 and SC-35. Further, we also investigated CaMKII activation, oxidative stress, and mitochondrial ultrastructure. In addition, wild-type mice were administered with a recombinant adeno-associated virus (AAV) carrying RIPK3, followed by TAC surgery to construct a model of myocardial hypertrophy, and the above-mentioned indicators were tested after 3 weeks. The results showed that RIPK3 deficiency could alleviate cardiac dysfunction, myocardial injury, aggravation of necrosis, and CaMKII activation induced by TAC surgery in mice with myocardial hypertrophy. Tail vein injection of AAV could reverse cardiac dysfunction, myocardial damage, aggravation of necrosis, and CaMKII activation in mice with myocardial hypertrophy. These results proved that RIPK3 could be used as a molecular intervention target for the prevention and treatment of myocardial hypertrophy. Full article

(This article belongs to the Special Issue Cardiac Diseases: Molecular Pathology, Diagnostics, and Therapeutics)

► Show Figures

Figure 1

25 pages, 5219 KiB

Open AccessArticle

Tankyrase Inhibition Attenuates Cardiac Dilatation and Dysfunction in Ischemic Heart Failure

by Hong Wang, Heli Segersvärd, Juuso Siren, Sanni Perttunen, Katariina Immonen, Riikka Kosonen, Yu-Chia Chen, Johanna Tolva, Mirjami Laivuori, Mikko I. Mäyränpää, Petri T. Kovanen, Juha Sinisalo, Mika Laine, Ilkka Tikkanen and Päivi Lakkisto

Int. J. Mol. Sci. 2022, 23(17), 10059; https://doi.org/10.3390/ijms231710059 - 02 Sep 2022

Cited by 2 | Viewed by 1852

Abstract

Hyperactive poly(ADP-ribose) polymerases (PARP) promote ischemic heart failure (IHF) after myocardial infarction (MI). However, the role of tankyrases (TNKSs), members of the PARP family, in pathogenesis of IHF remains unknown. We investigated the expression and activation of TNKSs in myocardium of IHF patients and MI rats. We explored the cardioprotective effect of TNKS inhibition in an isoproterenol-induced zebrafish HF model. In IHF patients, we observed elevated TNKS2 and DICER and concomitant upregulation of miR-34a-5p and miR-21-5p in non-infarcted myocardium. In a rat MI model, we found augmented TNKS2 and DICER in the border and infarct areas at the early stage of post-MI. We also observed consistently increased TNKS1 in the border and infarct areas and destabilized AXIN in the infarct area from 4 weeks onward, which in turn triggered Wnt/β-catenin signaling. In an isoproterenol-induced HF zebrafish model, inhibition of TNKS activity with XAV939, a TNKSs-specific inhibitor, protected against ventricular dilatation and cardiac dysfunction and abrogated overactivation of Wnt/β-catenin signaling and dysregulation of miR-34a-5p induced by isoproterenol. Our study unravels a potential role of TNKSs in the pathogenesis of IHF by regulating Wnt/β-catenin signaling and possibly modulating miRNAs and highlights the pharmacotherapeutic potential of TNKS inhibition for prevention of IHF. Full article

(This article belongs to the Special Issue Cardiac Diseases: Molecular Pathology, Diagnostics, and Therapeutics)

► Show Figures

Graphical abstract

15 pages, 7702 KiB

Open AccessArticle

Exosomal microRNAs miR-30d-5p and miR-126a-5p Are Associated with Heart Failure with Preserved Ejection Fraction in STZ-Induced Type 1 Diabetic Rats

by Jiung-Pang Huang, Chih-Chun Chang, Chao-Yu Kuo, Kuang-Jing Huang, Etienne M. Sokal, Kuan-Hsing Chen and Li-Man Hung

Int. J. Mol. Sci. 2022, 23(14), 7514; https://doi.org/10.3390/ijms23147514 - 06 Jul 2022

Cited by 13 | Viewed by 3343

Abstract

Exosomal microRNAs (EXO-miRNAs) are promising non-invasive diagnostic biomarkers for cardiovascular disease. Heart failure with preserved ejection fraction (HFpEF) is a poorly understood cardiovascular complication of diabetes mellitus (DM). Little is known about whether EXO-miRNAs can be used as biomarkers for HFpEF in DM. We aimed to investigate the relationship between EXO-miRNAs and HFpEF in STZ-induced diabetic rats. We prepared STZ-induced diabetic rats exhibiting a type 1 DM phenotype with low body weight, hyperglycemia, hyperlipidemia and hypoinsulinemia. Histological sections confirmed atrophy and fibrosis of the heart, with collagen accumulation representing diabetic cardiomyopathy. Significant decreases in end-diastolic volume, stroke volume, stroke work, end-systolic elastance and cardiac output indicated impaired cardiac contractility, as well as mRNA conversion of two isoforms of myosin heavy chain (α-MHC and β-MHC) and increased atrial natriuretic factor (ANF) mRNA indicating heart failure, were consistent with the features of HFpEF. In diabetic HFpEF rats, we examined a selected panel of 12 circulating miRNAs associated with HF (miR-1-3p, miR-21-5p, miR-29a-5p, miR-30d-5p, miR-34a-5p, miR-126a-5p, miR-143-3p, miR-145-5p, miR-195-5p, miR-206-3p, miR-320-3p and miR-378-3p). Although they were all expressed at significantly lower levels in the heart compared to non-diabetic controls, only six miRNAs (miR-21-5p, miR-30d-5p, miR-126a-5p, miR-206-3p, miR-320-3p and miR-378-3p) were also reduced in exosomal content, while one miRNA (miR-34a-5p) was upregulated. Similarly, although all miRNAs were correlated with reduced cardiac output as a measure of cardiovascular performance, only three miRNAs (miR-30d-5p, miR-126a-5p and miR-378-3p) were correlated in exosomal content. We found that miR-30d-5p and miR-126a-5p remained consistently correlated with significant reductions in exosomal expression, cardiac expression and cardiac output. Our findings support their release from the heart and association with diabetic HFpEF. We propose that these two EXO-miRNAs may be important for the development of diagnostic tools for diabetic HFpEF. Full article

(This article belongs to the Special Issue Cardiac Diseases: Molecular Pathology, Diagnostics, and Therapeutics)

► Show Figures

Graphical abstract

Review

Jump to: Research

11 pages, 843 KiB

Open AccessReview

Are Non-Invasive Modalities for the Assessment of Atherosclerosis Useful for Heart Failure Predictions?

by Kazuhiro Osawa and Toru Miyoshi

Int. J. Mol. Sci. 2023, 24(3), 1925; https://doi.org/10.3390/ijms24031925 - 18 Jan 2023

Cited by 1 | Viewed by 1719

Abstract

Heart failure (HF) is becoming an increasingly common issue worldwide and is associated with significant morbidity and mortality, making its prevention an important clinical goal. The criteria evaluated using non-invasive modalities such as coronary artery calcification, the ankle-brachial index, and carotid intima-media thickness have been proven to be effective in determining the relative risk of atherosclerotic cardiovascular disease. Notably, risk assessments using these modalities have been proven to be superior to the traditional risk predictors of cardiovascular disease. However, the ability to assess HF risk has not yet been well-established. In this review, we describe the clinical significance of such non-invasive modalities of atherosclerosis assessments and examine their ability to assess HF risk. The predictive value could be influenced by the left ventricular ejection fraction. Specifically, when the ejection fraction is reduced, its predictive value increases because this condition is potentially a result of coronary artery disease. In contrast, using these measures to predict HF with a preserved ejection fraction may be difficult because it is a heterogeneous condition. To overcome this issue, further research, especially on HF with a preserved ejection fraction, is required. Full article

(This article belongs to the Special Issue Cardiac Diseases: Molecular Pathology, Diagnostics, and Therapeutics)

► Show Figures

Figure 1

25 pages, 1253 KiB

Open AccessReview

Oncometabolism: A Paradigm for the Metabolic Remodeling of the Failing Heart

by Annika-Ricarda Kuhn and Marc van Bilsen

Int. J. Mol. Sci. 2022, 23(22), 13902; https://doi.org/10.3390/ijms232213902 - 11 Nov 2022

Cited by 2 | Viewed by 1841

Abstract

Heart failure is associated with profound alterations in cardiac intermediary metabolism. One of the prevailing hypotheses is that metabolic remodeling leads to a mismatch between cardiac energy (ATP) production and demand, thereby impairing cardiac function. However, even after decades of research, the relevance of metabolic remodeling in the pathogenesis of heart failure has remained elusive. Here we propose that cardiac metabolic remodeling should be looked upon from more perspectives than the mere production of ATP needed for cardiac contraction and relaxation. Recently, advances in cancer research have revealed that the metabolic rewiring of cancer cells, often coined as oncometabolism, directly impacts cellular phenotype and function. Accordingly, it is well feasible that the rewiring of cardiac cellular metabolism during the development of heart failure serves similar functions. In this review, we reflect on the influence of principal metabolic pathways on cellular phenotype as originally described in cancer cells and discuss their potential relevance for cardiac pathogenesis. We discuss current knowledge of metabolism-driven phenotypical alterations in the different cell types of the heart and evaluate their impact on cardiac pathogenesis and therapy. Full article

(This article belongs to the Special Issue Cardiac Diseases: Molecular Pathology, Diagnostics, and Therapeutics)

► Show Figures