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Biomolecules
Special Issues
Cellular and Molecular Mechanisms in Cardiopathy and Therapeutic Strategies
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Cellular and Molecular Mechanisms in Cardiopathy and Therapeutic Strategies

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 31 January 2026 | Viewed by 6745

Special Issue Editors

Dr. Ying-Hsi Lin

E-Mail Website
Guest Editor
Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore
Interests: cardiac physiology; cardiomyopathy; muscle mechanics; diastolic heart failures; mitochondrial biology
Special Issues, Collections and Topics in MDPI journals
Dr. Shengjie Lu

E-Mail Website
Guest Editor
National Heart Centre Singapore, Singapore 169609, Singapore
Interests: drug delivery; bioengineering; biomacromolecule and tissue engineering; cardiac medical device; nanomedicine and cardiac-targeting therapy

Special Issue Information

Dear Colleagues,

Cardiovascular disease (CVD), specifically heart failure (HF), is the leading cause of death globally and imposes a significant economic burden on the heartcare system. Despite current advances in the standard of care, the risk of death and the rehospitalization of HF patients remain unacceptably high. Notably, different forms of cardiopathies, defined as any sort of cardiac disease caused by maladaptive cardiac remodelling, impaired myocardial mechanics, and/or energetics, are often exposed along with the onset of HF symptoms and could act as potential targets to limit HF progression. Current treatments for cardiopathy include lifestyle changes, medications, and surgical or implantable devices, and with the advance in genome engineering, gene correction therapy for cardiomyopathy becomes promising. The primary objective of this Special Issue is to clarify our current understanding of the underlying mechanisms responsible for cardiopathy, preferably at cellular and molecular levels, that leads to HF and to explore the therapeutic strategies across interdisciplinary fields of biochemistry, biology, and engineering. We eagerly anticipate receiving your submissions and look forward to compiling an informative and insightful collection of articles.

Dr. Ying-Hsi Lin
Dr. Shengjie Lu
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. Biomolecules 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 2700 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

  • heart failure
  • cardiac remodelling
  • contractile dysfunction
  • bioenergetics
  • gene replacement or editing

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Published Papers (7 papers)

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Research

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20 pages, 11750 KB  
Article
Trandolapril Attenuates Pro-Arrhythmic Downregulation of Cx43 and Cx40 in Atria of Volume Overloaded Hypertensive and Normotensive Rats
by Matúš Sýkora, Katarína Ondreják Andelová, Alexandra Mrvová, Barbara Szeiffová Bačová and Narcis Tribulová
Biomolecules 2025, 15(10), 1457; https://doi.org/10.3390/biom15101457 - 15 Oct 2025
Viewed by 389
Abstract
Pressure overload in non-treated or resistant hypertension (HTN) increases the risk of heart failure (HF) as well as the occurrence of fatal ventricular arrhythmias and stroke-provoking atrial fibrillation (AF), while perturbed connexin-43 (Cx43) and Cx40 might be involved. In addition, kidney dysfunction may [...] Read more.
Pressure overload in non-treated or resistant hypertension (HTN) increases the risk of heart failure (HF) as well as the occurrence of fatal ventricular arrhythmias and stroke-provoking atrial fibrillation (AF), while perturbed connexin-43 (Cx43) and Cx40 might be involved. In addition, kidney dysfunction may facilitate hemodynamic volume overload and congestive HF. We investigated the impact of volume overload on Cx43 and Cx40 in right and left heart atria of hypertensive pressure overloaded Ren-2 transgenic (TGR) strain and normotensive Hannover Sprague Dawley (HSD) rats, as well as the efficacy of renin–angiotensin blockade with trandolapril and losartan. Key novel findings revealed lower levels of Cx43 and Cx40 proteins in left as well as right heart atria in pressure overloaded hypertensive rats compared to normotensive rats. There was a significant decrease in Cx43 and Cx40 proteins due to volume overload in both atria of normotensive as well as hypertensive rats. Treatment with trandolapril increased Cx43 and Cx40 levels in right and left heart atria of normotensive as well as hypertensive volume overloaded rats. While losartan increased Cx43 and did not affect Cx40 in left and right heart atria of volume overloaded rats. Findings of this study point out that right heart atria of normotensive as well as hypertensive rats are more susceptible to volume overload comparing to the left heart atria. Trandolapril attenuated pro-arrhythmic downregulation of Cx43 and Cx40 in atria of volume overloaded normotensive as well as hypertensive rats. This fact as well as examining AF inducibility requires further investigation. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Cardiopathy and Therapeutic Strategies)
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13 pages, 8923 KB  
Article
Supercomplex Restructuring in Heart Mitochondria of COX7A1-Deficient Mice
by Lauren Pavelich, Lucynda Pham, Paul Stemmer, Icksoo Lee, Lawrence I. Grossman, Maik Hüttemann and Tasnim Arroum
Biomolecules 2025, 15(9), 1209; https://doi.org/10.3390/biom15091209 - 22 Aug 2025
Viewed by 751
Abstract
The role of electron transport chain supercomplexes and factors that regulate their composition in a tissue- and species-specific manner are not fully understood. Tissue-specific isoforms have been reported for cytochrome c oxidase (COX), which may contribute to such regulation. Therefore, we here investigated [...] Read more.
The role of electron transport chain supercomplexes and factors that regulate their composition in a tissue- and species-specific manner are not fully understood. Tissue-specific isoforms have been reported for cytochrome c oxidase (COX), which may contribute to such regulation. Therefore, we here investigated COX activity and structural organization in wild-type (WT) and COX7A1 knockout (KO) mice, which lack the heart/skeletal muscle isoform of COX subunit VIIa. COX7A1 KO mice showed a 30% reduction in total COX activity in the heart. Although the activity of COX in the monomers and I+III2+IVn supercomplexes (SCs) remained unchanged, a marked reduction in COX dimers and unknown COX-containing species IVx and IVy contributed to the overall reduction in COX activity. Furthermore, we observed that COX7A2 substituted for COX7A1 in COX monomers, dimers, and all COX-containing SCs in the KO mice, indicating a compensatory mechanism to preserve COX functionality. Collectively, these results suggest that COX7A1 plays an important role in maintaining structural stability; however, they also suggest that loss of COX7A1 is compensated by its replacement with COX7A2. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Cardiopathy and Therapeutic Strategies)
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Review

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22 pages, 1018 KB  
Review
Molecular Pathogenesis of Arrhythmogenic Cardiomyopathy: Mechanisms and Therapeutic Perspectives
by Eliza Popa and Sorin Hostiuc
Biomolecules 2025, 15(11), 1512; https://doi.org/10.3390/biom15111512 - 25 Oct 2025
Viewed by 538
Abstract
Arrhythmogenic cardiomyopathy (ACM) is a genetic cardiac disease characterized by a progressive loss of cardiomyocytes associated with fibrofatty myocardial replacement, resulting in a heightened risk of ventricular arrhythmias and sudden cardiac death. ACM is a common cause of sudden death in young individuals, [...] Read more.
Arrhythmogenic cardiomyopathy (ACM) is a genetic cardiac disease characterized by a progressive loss of cardiomyocytes associated with fibrofatty myocardial replacement, resulting in a heightened risk of ventricular arrhythmias and sudden cardiac death. ACM is a common cause of sudden death in young individuals, and exercise has been proven to be a factor in disease progression. Current therapeutic strategies, including lifestyle modification, antiarrhythmic pharmacological therapy, catheter ablation, and the placement of implantable cardioverter-defibrillators, remain primarily palliative options rather than addressing the underlying molecular substrate. The pathogenesis of ACM includes complex molecular and cellular mechanisms, linking genetic mutations to structural and electrical anomalies of the ventricle. The lack of targeted therapies contributes to a challenging approach to the disease. It highlights the need for a better understanding of the mechanisms that lead to myocardial remodeling and arrhythmic predisposition. With the help of animal models (especially murine) and induced pluripotent stem cells, there have been advances in understanding the molecular pathogenesis of ACM. In this review, we summarized some of the pathogenic molecular pathways involved in the development of ACM and emerging therapies targeted towards disease modification, not just prevention. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Cardiopathy and Therapeutic Strategies)
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12 pages, 240 KB  
Review
Inflammatory Mechanisms in Myocarditis—Recent Therapeutic Strategies
by Stergios Soulaidopoulos, Dimitris Tousoulis, Marios Sagris, Svetlana Aghayan, Konstantinos Platanias, Alexios Giannakodimos, Emilia Lazarou, Konstantinos Tsioufis and George Lazaros
Biomolecules 2025, 15(10), 1475; https://doi.org/10.3390/biom15101475 - 20 Oct 2025
Viewed by 577
Abstract
Myocarditis is an inflammatory disease of the heart characterized by a complex interplay between innate and adaptive immune responses. The innate immune system provides first-line defense and includes soluble molecules, including macrophages, neutrophils, dendritic cells, and molecular mediators, but lacks immunological memory. In [...] Read more.
Myocarditis is an inflammatory disease of the heart characterized by a complex interplay between innate and adaptive immune responses. The innate immune system provides first-line defense and includes soluble molecules, including macrophages, neutrophils, dendritic cells, and molecular mediators, but lacks immunological memory. In contrast, the adaptive immune system, via T and B lymphocytes, offers high specificity and long-term memory, which can sometimes target myocardial tissue, causing autoimmune injury. Particularly, acute myocarditis is characterized by dysregulated immune signaling, with cytokines (IL-2, IFN-γ, IL-12, IL-4, IL-10) and chemokines (MCP-1, CXCL4, CXCL10) driving disease progression, while adhesion molecules (ICAM-1, VCAM-1, VAP-1) promote leukocyte trafficking and cardiac inflammation. The balance between pro-inflammatory and regulatory responses determines disease outcomes, ranging from resolution with recovery to fulminant myocarditis or progression to dilated cardiomyopathy. Emerging therapeutic approaches targeting cytokines, chemokines, and adhesion molecules, along with established immunosuppressive treatments, underline the potential for modulating immune responses in myocarditis and, thereby, improving patient outcomes. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Cardiopathy and Therapeutic Strategies)
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29 pages, 2056 KB  
Review
From Gut to Heart: Targeting Trimethylamine N-Oxide as a Novel Strategy in Heart Failure Management
by Zehui Ding, Yunfeng Yu, Jiaming Wei, Ziyan Wang, Ruifang Lin, Ya Li and Zhihua Guo
Biomolecules 2025, 15(10), 1447; https://doi.org/10.3390/biom15101447 - 13 Oct 2025
Viewed by 886
Abstract
Heart failure (HF) marks the culmination of numerous cardiac pathologies, presenting a major medical hurdle in prevention and treatment. In recent years, with the advancements in genomics and metabolomics, research has demonstrated that gut microbiota plays a significant role in the pathogenesis of [...] Read more.
Heart failure (HF) marks the culmination of numerous cardiac pathologies, presenting a major medical hurdle in prevention and treatment. In recent years, with the advancements in genomics and metabolomics, research has demonstrated that gut microbiota plays a significant role in the pathogenesis of HF. Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite and primarily sourced from foods abundant in choline, L-carnitine, and betaine. Research has shown that patients with HF exhibit higher levels of TMAO. Accumulating evidence has indicated that TMAO directly or indirectly mediates the occurrence and development of HF through multiple mechanisms. Furthermore, TMAO functions as a crucial prognostic marker in HF. Therefore, TMAO emerges as a potential therapeutic target for HF. This article reviews the generation and metabolic pathways of TMAO, emphasizes its pathophysiological mechanisms in HF, and explores promising therapeutic approaches targeting TMAO, offering novel insights and strategies for HF management. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Cardiopathy and Therapeutic Strategies)
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21 pages, 1786 KB  
Review
Aortic Stiffness and Alzheimer’s Disease: The Medin Connection
by Filippos Triposkiadis, Andrew Xanthopoulos, Harisios Boudoulas and Dirk L. Brutsaert
Biomolecules 2025, 15(8), 1148; https://doi.org/10.3390/biom15081148 - 8 Aug 2025
Viewed by 1123
Abstract
Aging is associated with aortic stiffening (AoSt), a condition characterized by diminished aortic elasticity that predisposes individuals to cognitive decline, including Alzheimer’s disease (AD). Emerging evidence implicates medin, which is derived from milk fat globule-EGF factor 8 protein (MFG-E8), as a key link [...] Read more.
Aging is associated with aortic stiffening (AoSt), a condition characterized by diminished aortic elasticity that predisposes individuals to cognitive decline, including Alzheimer’s disease (AD). Emerging evidence implicates medin, which is derived from milk fat globule-EGF factor 8 protein (MFG-E8), as a key link between AoSt and AD. Medin aggregates into aortic medial amyloid (AMA), which is found in approximately 97% of Caucasian individuals aged 50 and above, contributing to vascular inflammation, calcification, and loss of arterial elasticity. These changes may promote hyperpulsatile cerebral blood flow and impair glymphatic clearance, resulting in increased deposition of neurotoxic proteins, such as amyloid-β (Aβ) and possibly medin, which colocalizes with vascular Aβ in the brain. Medin enhances Aβ aggregation, generating heterologous fibrils, and thereby contributes to cerebrovascular dysfunction and neuroinflammation. This interaction (cross-seeding) may deteriorate amyloid pathology in both the vasculature and the parenchyma in AD. Furthermore, medin per se causes endothelial dysfunction, increases oxidative stress, and activates glial cells, promoting the development of a pro-inflammatory environment that enhances cognitive decline. In this manuscript, we contend that medin might act as a bridge connecting the age-related increase in aortic stiffness to AD, and therefore, medin might present a novel therapeutic target within this context. This hypothesis deserves experimental and clinical validation. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Cardiopathy and Therapeutic Strategies)
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16 pages, 1138 KB  
Review
Cardiac Myosin Inhibitors in the Treatment of Hypertrophic Cardiomyopathy: Clinical Trials and Future Challenges
by Arnold Kukowka and Marek Droździk
Biomolecules 2025, 15(8), 1098; https://doi.org/10.3390/biom15081098 - 29 Jul 2025
Viewed by 1865
Abstract
Hypertrophic cardiomyopathy (HCM) is a prevalent and often underdiagnosed genetic cardiac disorder characterized by left ventricular hypertrophy and, in many cases, dynamic left ventricular outflow tract obstruction (LVOTO). The development of cardiac myosin inhibitors (CMIs) represents an emerging therapeutic approach in the pharmacological [...] Read more.
Hypertrophic cardiomyopathy (HCM) is a prevalent and often underdiagnosed genetic cardiac disorder characterized by left ventricular hypertrophy and, in many cases, dynamic left ventricular outflow tract obstruction (LVOTO). The development of cardiac myosin inhibitors (CMIs) represents an emerging therapeutic approach in the pharmacological management of obstructive HCM (oHCM). This review offers an integrated and up-to-date synthesis of the cardiac myosin inhibitor class, with a focus on mavacamten, aficamten, and the broader landscape of emerging agents. It also highlights recent clinical trial outcomes, pharmacokinetic and pharmacogenetic considerations, and potential future directions in therapy. Furthermore, we incorporate the most recent data up to May 2025, including late-breaking trial results and real-world safety findings, aiming to provide clinicians with a practical and comprehensive perspective on this evolving drug class. A narrative review was conducted by systematically searching PubMed, Scopus, Google Scholar, and ClinicalTrials.gov for English-language articles and trials published between January 2016 and May 2025. Keywords included “cardiac myosin inhibitor”, mavacamten”, “aficamten”, “MYK-224”, and “hypertrophic cardiomyopathy.” Inclusion criteria encompassed clinical trials and comprehensive reviews specifically addressing CMIs in cardiac applications. CMIs such as mavacamten and aficamten have demonstrated significant clinical benefits in reducing LVOT gradients, improving exercise capacity, and alleviating symptoms in patients with oHCM. Mavacamten is currently approved for clinical use, while aficamten is in advanced regulatory review. Comparative data suggest potential advantages of aficamten in the onset of action, pharmacokinetic profile, and tolerability. Emerging evidence supports the exploration of CMIs in pediatric populations, heart failure with preserved ejection fraction (HFpEF), and non-obstructive HCM (nHCM), although results are still preliminary. Cardiac myosin inhibitors offer a novel, pathophysiology-targeted approach to managing oHCM. While mavacamten has established efficacy, next-generation agents like aficamten may offer improved safety and versatility. Further long-term studies are needed to clarify their role across broader patient populations. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Cardiopathy and Therapeutic Strategies)
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