International Journal of Molecular Sciences

Journal Browser

► Journal Browser

Cellular and Molecular Mechanisms of Myocardial Diseases

Share This Special Issue

Special Issue Editor

Dr. Jason K. Higa

E-Mail Website
Guest Editor

Department of Anatomy, Biochemistry & Physiology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA
Interests: endocrinology; metabolic disorders; cardiac physiology; medical education

Special Issue Information

Dear Colleagues,

Even though much is known about the heart and blood vessels, cardiovascular disease is still the leading cause of death around the world. Therefore, there is still a need to find further strategies to prevent, treat, and manage various cardiovascular diseases. Protecting cardiac tissue against cell death is a viable strategy for limiting damage to the heart. The myocardium performs the contraction and relaxation motions that drive circulation, making its protection a priority for preserving cardiac function in the face of cardiovascular disease. The discovery and elucidation of multiple forms of cell death beyond apoptosis has opened multiple avenues for preventing or limiting injury to the heart in cardiovascular disease.

Suitable topics for inclusion in this Special Issue include, but are not limited to, the following: apoptosis, necrosis, necroptosis, pyroptosis, ferroptosis, autophagy, or other mechanisms of cell injury and death in cardiomyocytes or myocardial tissue; preventative strategies that protect the myocardium against injury or cell death; and interventions that regenerate or restore cardiac function after myocardial injury.

Dr. Jason K. Higa
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.

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.

Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.

Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.

External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.

e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (2 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Review

33 pages, 4799 KiB

Open AccessReview

Autophagy and Its Association with Macrophages in Clonal Hematopoiesis Leading to Atherosclerosis

by Shuanhu Li, Xin Zhou, Qinchun Duan, Shukun Niu, Pengquan Li, Yihan Feng, Ye Zhang, Xuehong Xu, Shou-Ping Gong and Huiling Cao

Int. J. Mol. Sci. 2025, 26(7), 3252; https://doi.org/10.3390/ijms26073252 - 1 Apr 2025

Viewed by 790

Abstract

Atherosclerosis, a chronic inflammatory disease characterized by lipid accumulation and immune cell infiltration, is linked to plaque formation and cardiovascular events. While traditionally associated with lipid metabolism and endothelial dysfunction, recent research highlights the roles of autophagy and clonal hematopoiesis (CH) in its pathogenesis. Autophagy, a cellular process crucial for degrading damaged components, regulates macrophage homeostasis and inflammation, both of which are pivotal in atherosclerosis. In macrophages, autophagy influences lipid metabolism, cytokine regulation, and oxidative stress, helping to prevent plaque instability. Defective autophagy exacerbates inflammation, impairs cholesterol efflux, and accelerates disease progression. Additionally, autophagic processes in endothelial cells and smooth muscle cells further contribute to atherosclerotic pathology. Recent studies also emphasize the interplay between autophagy and CH, wherein somatic mutations in genes like TET2, JAK2, and DNMT3A drive immune cell expansion and enhance inflammatory responses in atherosclerotic plaques. These mutations modify macrophage function, intensifying the inflammatory environment and accelerating atherosclerosis. Chaperone-mediated autophagy (CMA), a selective form of autophagy, also plays a critical role in regulating macrophage inflammation by degrading pro-inflammatory cytokines and oxidized low-density lipoprotein (ox-LDL). Impaired CMA activity leads to the accumulation of these substrates, activating the NLRP3 inflammasome and worsening inflammation. Preclinical studies suggest that pharmacologically activating CMA may mitigate atherosclerosis progression. In animal models, reduced CMA activity accelerates plaque instability and increases inflammation. This review highlights the importance of autophagic regulation in macrophages, focusing on its role in inflammation, plaque formation, and the contributions of CH. Building upon current advances, we propose a hypothesis in which autophagy, programmed cell death, and clonal hematopoiesis form a critical intrinsic axis that modulates the fundamental functions of macrophages, playing a complex role in the development of atherosclerosis. Understanding these mechanisms offers potential therapeutic strategies targeting autophagy and inflammation to reduce the burden of atherosclerotic cardiovascular disease. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Myocardial Diseases)

► Show Figures

Figure 1

27 pages, 2769 KiB

Open AccessReview

Autophagy in High-Fat Diet and Streptozotocin-Induced Metabolic Cardiomyopathy: Mechanisms and Therapeutic Implications

by Rong Zhou, Zutong Zhang, Xinjie Li, Qinchun Duan, Yuanlin Miao, Tingting Zhang, Mofei Wang, Jiali Li, Wei Zhang, Liyang Wang, Odell D. Jones, Mengmeng Xu, Yingli Liu and Xuehong Xu

Int. J. Mol. Sci. 2025, 26(4), 1668; https://doi.org/10.3390/ijms26041668 - 15 Feb 2025

Cited by 1 | Viewed by 1664

Abstract

Metabolic cardiomyopathy, encompassing diabetic and obese cardiomyopathy, is an escalating global health concern, driven by the rising prevalence of metabolic disorders such as insulin resistance, type 1 and type 2 diabetes, and obesity. These conditions induce structural and functional alterations in the heart, including left ventricular dysfunction, fibrosis, and ultimately heart failure, particularly in the presence of coronary artery disease or hypertension. Autophagy, a critical cellular process for maintaining cardiac homeostasis, is frequently disrupted in metabolic cardiomyopathy. This review explores the role of autophagy in the pathogenesis of high-fat diet (HFD) and streptozotocin (STZ)-induced metabolic cardiomyopathy, focusing on non-selective and selective autophagy pathways, including mitophagy, ER-phagy, and ferritinophagy. Key proteins and genes such as PINK1, Parkin, ULK1, AMPK, mTOR, ATG7, ATG5, Beclin-1, and miR-34a are central to the regulation of autophagy in metabolic cardiomyopathy. Dysregulated autophagic flux impairs mitochondrial function, promotes oxidative stress, and drives fibrosis in the heart. Additionally, selective autophagy processes such as lipophagy, regulated by PNPLA8, and ferritinophagy, modulated by NCOA4, play pivotal roles in lipid metabolism and iron homeostasis. Emerging therapeutic strategies targeting autophagy, including plant extracts (e.g., curcumin, dihydromyricetin), endogenous compounds (e.g., sirtuin 3, LC3), and lipid/glucose-lowering drugs, offer promising avenues for mitigating the effects of metabolic cardiomyopathy. Despite recent advances, the precise mechanisms underlying autophagy in this context remain poorly understood. A deeper understanding of autophagy’s regulatory networks, particularly involving these critical genes and proteins, may lead to novel therapeutic approaches for treating metabolic cardiomyopathy. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Myocardial Diseases)

► Show Figures

Journal Menu

Journal Browser

Cellular and Molecular Mechanisms of Myocardial Diseases

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (2 papers)

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI