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Molecular Mechanisms of Cardiotoxicity

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

Deadline for manuscript submissions: 31 January 2025 | Viewed by 715

Special Issue Editor


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Guest Editor
Department of Medicine, University of Murcia, 30120 Murcia, Spain
Interests: myocardial infarction; adverse remodeling; heart failure; cardiotoxicity; cardiac dysfunction; ventricular remodeling; cardioprotection; ischemic heart disease; cardiomyopathy; cardiac regeneration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cardiotoxicity is heart damage that arises from certain cancer treatments or drugs. It can develop years after cancer treatment. Although the molecular mechanism related to chemotherapy-induced cardiotoxicity is associated with activation of oxidative stress in oncologic patients, studies with a more standardized design and better characterized populations are necessary to evaluate novel molecular axes. Further, the development of new technologies allows the analysis of a large volume of data, which may lead to enabling a more precise description of the molecular processes related to cardiotoxicity after chemotherapy.

Here, I propose an ambitious special issue to change the conceptual framework used for the management of cardiotoxicity. The aim will be to detail novel molecular mechanisms related to cardiotoxicity, with novel pharmacological targets described to design pioneering therapies to treat or prevent cardiotoxicity related to chemotherapeutic treatments.

Dr. Antonio Lax
Guest Editor

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Keywords

  • cardiac dysfunction
  • cardiotoxicity
  • atrophy
  • antagomiR
  • AAV
  • gene therapy
  • heart failure
  • oxidative stress
  • apoptosis
  • myocardial remodeling

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Published Papers (1 paper)

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Research

27 pages, 20721 KiB  
Article
Doxorubicin-Induced Cardiotoxicity Through SIRT1 Loss Potentiates Overproduction of Exosomes in Cardiomyocytes
by Shuai Zhang, Yu Yang, Xinchen Lv, Xue Zhou, Wangqian Zhao, Linfeng Meng, Hongfei Xu, Shaohua Zhu and Ying Wang
Int. J. Mol. Sci. 2024, 25(22), 12376; https://doi.org/10.3390/ijms252212376 - 18 Nov 2024
Viewed by 499
Abstract
Mutual interaction between doxorubicin (DOX) and cardiomyocytes is crucial for cardiotoxicity progression. Cardiomyocyte injury is an important pathological feature of DOX-induced cardiomyopathy, and its molecular pathogenesis is multifaceted. In addition to the direct toxic effects of DOX on cardiomyocytes, DOX-induced exosomes in the [...] Read more.
Mutual interaction between doxorubicin (DOX) and cardiomyocytes is crucial for cardiotoxicity progression. Cardiomyocyte injury is an important pathological feature of DOX-induced cardiomyopathy, and its molecular pathogenesis is multifaceted. In addition to the direct toxic effects of DOX on cardiomyocytes, DOX-induced exosomes in the extracellular microenvironment also regulate the pathophysiological states of cardiomyocytes. However, the mechanisms by which DOX regulates exosome secretion and subsequent pathogenesis remain incompletely understood. Here, we found that DOX significantly increased exosome secretion from cardiomyocytes, and inhibiting this release could alleviate cardiomyocyte injury. DOX promoted exosome secretion by reducing cardiomyocyte silencing information regulator 1 (SIRT1) expression, exacerbating cardiotoxicity. DOX impaired lysosomal acidification in cardiomyocytes, reducing the degradation of intracellular multivesicular bodies (MVBs), resulting in an increase in MVB volume before fusing with the plasma membrane to release their contents. Mechanistically, SIRT1 loss inhibited lysosomal acidification by reducing the expression of the ATP6V1A subunit of the lysosomal vacuolar-type H+ ATPase (V-ATPase) proton pump. Overexpressing SIRT1 increased ATP6V1A expression, improved lysosomal acidification, inhibited exosome secretion, and thereby alleviated DOX-induced cardiotoxicity. Interestingly, DOX also induced mitochondrial-derived vesicle formation in cardiomyocytes, which may further increase the abundance of MVBs and promote exosome release. Collectively, this study identified SIRT1-mediated impairment of lysosomal acidification as a key mechanism underlying the increased exosome secretion from cardiomyocytes induced by DOX, providing new insights into DOX-induced cardiotoxicity pathogenesis. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Cardiotoxicity)
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