Molecular and Cellular Mechanisms of Heart Disease

Topic Information

Dear Colleagues,

Heart failure is still a leading cause of mortality worldwide. Cardiomyocytes contribute to heart failure by losing the ability to generate sufficient force to pump blood into circulation. To improve the current treatment options in cardiology, it is important to have a better understanding of the biological behavior of cardiomyocytes. The function of these cells cannot be completely understood independently of the interaction with surrounding cells, i.e., cardiac fibroblasts and vascular cells. Nevertheless, cardiomyocytes are the cells that must generate heart work. They can modify parts of their electromechanical coupling machinery, electrometabolic coupling, or increase in size via hypertrophy. However, hypertrophy can be either adaptive or maladaptive, and the transition from the one into the other type of hypertrophy is not clearly understood. Pathological hypertrophy is often characterised by cardiac fibrosis and contributes to cardiac dysfunction. Cell death, i.e., cardiomyocyte apoptosis, is another common feature of heart disease. Processes dealing with metabolism and mitochondrial function, electromechanical coupling, cell death, and electrophysiological aspects are among the processes that need to be addressed and understood in their molecular fine regulation in order to improve treatment regimes.

This Topic aims to summarize the current understanding of the process of developing heart failure with a focus on the force-generating cell, the cardiomyocyte.

Prof. Dr. Pasi Tavi
Prof. Dr. Ebru Arioglu-Inan
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Current Issues in Molecular Biology cimb	2.8	2.9	1999	15.8 Days	CHF 2200	Submit
International Journal of Molecular Sciences ijms	4.9	8.1	2000	16.8 Days	CHF 2900	Submit
Journal of Cardiovascular Development and Disease jcdd	2.4	2.6	2014	25.7 Days	CHF 2700	Submit
Organoids organoids	-	-	2022	19.3 Days	CHF 1000	Submit
Biomedicines biomedicines	3.9	5.2	2013	14.6 Days	CHF 2600	Submit

Preprints.org is a multidisciplinary platform offering a preprint service designed to facilitate the early sharing of your research. It supports and empowers your research journey from the very beginning.

MDPI Topics is collaborating with Preprints.org and has established a direct connection between MDPI journals and the platform. Authors are encouraged to take advantage of this opportunity by posting their preprints at Preprints.org prior to publication:

1. Share your research immediately: disseminate your ideas prior to publication and establish priority for your work.
2. Safeguard your intellectual contribution: Protect your ideas with a time-stamped preprint that serves as proof of your research timeline.
3. Boost visibility and impact: Increase the reach and influence of your research by making it accessible to a global audience.
4. Gain early feedback: Receive valuable input and insights from peers before submitting to a journal.
5. Ensure broad indexing: Web of Science (Preprint Citation Index), Google Scholar, Crossref, SHARE, PrePubMed, Scilit and Europe PMC.

Published Papers (4 papers)

Order results

Content type Publication Date

Result details

Normal Extended Compact

Journals

All CIMB IJMS JCDD Organoids Biomedicines

Show export options expand_more Show export options expand_less

Select all

Export citation of selected articles as:

Plain Text BibTeX BibTeX (without abstracts) Endnote Endnote (without abstracts) Tab-delimited RIS

Error

Oops... you haven't selected anything for export.

Ok

clear

20 pages, 2409 KiB  

Open AccessReview

The Mechanical Role of YAP/TAZ in the Development of Diabetic Cardiomyopathy

by Jun-Xian Shen, Ling Zhang, Huan-Huan Liu, Zhen-Ye Zhang, Ning Zhao, Jia-Bin Zhou, Ling-Ling Qian and Ru-Xing Wang

Curr. Issues Mol. Biol. 2025, 47(5), 297; https://doi.org/10.3390/cimb47050297 - 23 Apr 2025

Abstract

Diabetic cardiomyopathy (DCM) begins with a subclinical stage featuring cardiac hypertrophy, fibrosis, and disrupted signaling. These changes, especially fibrosis and stiffness, often lead to clinical heart failure. The mechanism involves metabolic dysregulation, oxidative stress, and inflammation, leading to cardiac damage and dysfunction. During [...] Read more.

Diabetic cardiomyopathy (DCM) begins with a subclinical stage featuring cardiac hypertrophy, fibrosis, and disrupted signaling. These changes, especially fibrosis and stiffness, often lead to clinical heart failure. The mechanism involves metabolic dysregulation, oxidative stress, and inflammation, leading to cardiac damage and dysfunction. During the progression of the disease, the myocardium senses surrounding mechanical cues, including extracellular matrix properties, tensile tension, shear stress, and pressure load, which significantly influence the pathological remodeling of the heart through mechanotransduction. At the molecular level, the mechanisms by which mechanical cues are sensed and transduced to mediate myocardial mechanical remodeling in DCM remain unclear. The mechanosensitive transcription factors YAP and TAZ fill this gap. This article reviews the latest findings of how YAP and TAZ perceive a wide range of mechanical cues, from shear stress to extracellular matrix stiffness. We focus on how these cues are relayed through the cytoskeleton to the nucleus, where they trigger downstream gene expression. Here, we review recent progress on the crucial role of YAP and TAZ mechanotransduction in the pathological changes observed in DCM, including myocardial fibrosis, hypertrophy, inflammation, mitochondrial dysfunction, and cell death. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Heart Disease)

►▼ Show Figures

Graphical abstract

29 pages, 1249 KiB  

Open AccessReview

The Application and Molecular Mechanisms of Mitochondria-Targeted Antioxidants in Chemotherapy-Induced Cardiac Injury

by Chih-Jen Liu, Lu-Kai Wang and Fu-Ming Tsai

Curr. Issues Mol. Biol. 2025, 47(3), 176; https://doi.org/10.3390/cimb47030176 - 7 Mar 2025

Viewed by 905

Abstract

Chemotherapeutic agents play a crucial role in cancer treatment. However, their use is often associated with significant adverse effects, particularly cardiotoxicity. Drugs such as anthracyclines (e.g., doxorubicin) and platinum-based agents (e.g., cisplatin) cause mitochondrial damage, which is one of the main mechanisms underlying [...] Read more.

Chemotherapeutic agents play a crucial role in cancer treatment. However, their use is often associated with significant adverse effects, particularly cardiotoxicity. Drugs such as anthracyclines (e.g., doxorubicin) and platinum-based agents (e.g., cisplatin) cause mitochondrial damage, which is one of the main mechanisms underlying cardiotoxicity. These drugs induce oxidative stress, leading to an increase in reactive oxygen species (ROS), which in turn damage the mitochondria in cardiomyocytes, resulting in impaired cardiac function and heart failure. Mitochondria-targeted antioxidants (MTAs) have emerged as a promising cardioprotective strategy, offering a potential solution. These agents efficiently scavenge ROS within the mitochondria, protecting cardiomyocytes from oxidative damage. Recent studies have shown that MTAs, such as elamipretide, SkQ1, CoQ10, and melatonin, significantly mitigate chemotherapy-induced cardiotoxicity. These antioxidants not only reduce oxidative damage but also help maintain mitochondrial structure and function, stabilize mitochondrial membrane potential, and prevent excessive opening of the mitochondrial permeability transition pore, thus preventing apoptosis and cardiac dysfunction. In this review, we integrate recent findings to elucidate the mechanisms of chemotherapy-induced cardiotoxicity and highlight the substantial therapeutic potential of MTAs in reducing chemotherapy-induced heart damage. These agents are expected to offer safer and more effective treatment options for cancer patients in clinical practice. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Heart Disease)

►▼ Show Figures

Figure 1

attachment

Supplementary material:
Supplementary File 1 (ZIP, 2111 KiB)

23 pages, 7444 KiB  

Open AccessArticle

Monocyte/Macrophage-Specific Loss of ARNTL Suppresses Chronic Kidney Disease-Associated Cardiac Impairment

by Yuya Yoshida, Naoki Nishikawa, Kohei Fukuoka, Akito Tsuruta, Kaita Otsuki, Taiki Fukuda, Yuma Terada, Tomohito Tanihara, Taisei Kumamoto, Ryotaro Tsukamoto, Takumi Nishi, Kosuke Oyama, Kengo Hamamura, Kouta Mayanagi, Satoru Koyanagi, Shigehiro Ohdo and Naoya Matsunaga

Int. J. Mol. Sci. 2024, 25(23), 13009; https://doi.org/10.3390/ijms252313009 - 3 Dec 2024

Cited by 1 | Viewed by 1305

Abstract

Defects in Aryl hydrocarbon receptor nuclear translocator-like 1 (ARNTL), a central component of the circadian clock mechanism, may promote or inhibit the induction of inflammation by monocytes/macrophages, with varying effects on different diseases. However, ARNTL’s role in monocytes/macrophages under chronic kidney disease (CKD), [...] Read more.

Defects in Aryl hydrocarbon receptor nuclear translocator-like 1 (ARNTL), a central component of the circadian clock mechanism, may promote or inhibit the induction of inflammation by monocytes/macrophages, with varying effects on different diseases. However, ARNTL’s role in monocytes/macrophages under chronic kidney disease (CKD), which presents with systemic inflammation, is unclear. Here, we report that the expression of Arntl in monocytes promoted CKD-induced cardiac damage. The expression of G-protein-coupled receptor 68 (GPR68), which exacerbates CKD-induced cardiac disease, was regulated by ARNTL. Under CKD conditions, GPR68 expression was elevated via ARNTL, particularly in the presence of PU.1, a transcription factor specific to monocytes and macrophages. In CKD mouse models lacking monocyte-specific ARNTL, GPR68 expression in monocytes was reduced, leading to decreased cardiac damage and fibrosis despite no improvement in renal excretory capacity or renal fibrosis and increased angiotensin II production. The loss of ARNTL did not affect the expression of marker molecules, indicating the origin or differentiation of cardiac macrophages, but affected GPR68 expression only in cardiac macrophages derived from mature monocytes, highlighting the significance of the interplay between GPR68 and ARNTL in monocytes/macrophages and its influence on cardiac pathology. Understanding this complex relationship between circadian clock mechanisms and disease could help uncover novel therapeutic strategies. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Heart Disease)

►▼ Show Figures

Figure 1

12 pages, 694 KiB  

Open AccessArticle

A Multi-Biomarker Approach to Increase the Accuracy of Diagnosis and Management of Coronary Artery Disease

by Lenka Hostačná, Jana Mašlanková, Dominik Pella, Beáta Hubková, Mária Mareková and Daniel Pella

J. Cardiovasc. Dev. Dis. 2024, 11(9), 258; https://doi.org/10.3390/jcdd11090258 - 23 Aug 2024

Cited by 1 | Viewed by 1498

Abstract

Non-invasive possibilities of predicting cardiovascular risk and monitoring the treatment and progression of coronary artery disease (CAD) are important subjects of cardiovascular research. Various inflammatory markers have been identified as potential biomarkers of CAD, including interleukin-6 (IL-6), lipocalin-2 (LCN-2), growth differentiation factor 15 [...] Read more.

Non-invasive possibilities of predicting cardiovascular risk and monitoring the treatment and progression of coronary artery disease (CAD) are important subjects of cardiovascular research. Various inflammatory markers have been identified as potential biomarkers of CAD, including interleukin-6 (IL-6), lipocalin-2 (LCN-2), growth differentiation factor 15 (GDF-15), and T cell immunoglobulin and mucin domain-3 (TIM-3). This research aims to identify their utility in the investigation of CAD severity and progression. The basic anthropometric parameters, as well as the levels of urea, creatinine, CRP, leukocytes, fibrinogen, and biomarkers of inflammation, were measured in 130 patients who underwent coronary angiography. In male patients, divided according to findings on coronary angiography, we observed an increasing expression of GDF-15 with increasing stenosis (with worsening findings). In females, we observed increasing fibrinogen expression with increasing stenosis, i.e., findings on coronary angiography. Correlation analysis did not confirm the relationship between TIM-3, LCN and 2, IL-6 and the severity of findings obtained by coronary angiography; however, the correlation of TIM-3 and LCN-2 expression was positive with the finding, and the correlation of IL-6 with the finding was surprisingly negative. Understanding the role of these inflammatory markers in CAD can be helpful in risk stratification, guiding therapeutic strategies, and monitoring treatment responses in patients with CAD. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Heart Disease)

►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less

Select all

Export citation of selected articles as:

Plain Text BibTeX BibTeX (without abstracts) Endnote Endnote (without abstracts) Tab-delimited RIS

 

Error

Oops... you haven't selected anything for export.

Ok

clear

Displaying articles 1-4