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Therapeutic Strategy for Pathological Cardiac Hypertrophy

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

Deadline for manuscript submissions: closed (22 August 2023) | Viewed by 3566

Special Issue Editor


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Guest Editor
Insitute of Clinical Physiology, National Research Council (IFC-CNR), 56124 Pisa, Italy
Interests: preclinical models; in vivo models of cardiac hypertrophy and cardiotoxicity; cardiovascular disease; obesity; mitochondrial damage; cardio-oncology
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Special Issue Information

Dear Colleagues,

Pathological cardiac hypertrophy is a key risk factor for heart failure. Increased interstitial fibrosis, cardiac dysfunction and cell death are essential features of pathological cardiac hypertrophy. The numerous mediators that have been found as involved in the pathogenesis of maladaptive heart growth can affect gene transcription, calcium handling, protein synthesis, metabolism, mitochondrial function, autophagy, oxidative stress and inflammation. Many of the molecular mechanisms and dysregulated signaling pathways implicated in promoting malignant remodeling have been unrevealed. Focusing on these key regulation points seems to be an important target for defining innovative strategies for the management of pathological hypertrophy.

This special issue aims to take stock of advances in the development and validation of therapeutic strategies against pathological cardiac hypertrophy, both in preclinical and clinical studies. Research papers and up-to-date review articles are all welcome on various topics including, but not limited to, either conventional drug strategies or novel therapeutic approaches (e.g., RNA-based therapies, dietary supplementation, drug delivery systems) targeting molecular pathways involved in the transition to hypertrophic maladaptive remodeling of the heart.

Dr. Claudia Kusmic
Guest Editor

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Keywords

  • myocardial hypertrophy
  • cardiac remodeling
  • heart failure
  • drug therapy
  • molecular therapeutic targets
  • myocardial gene therapy

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Published Papers (1 paper)

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Research

19 pages, 6397 KiB  
Article
GPR30 Alleviates Pressure Overload-Induced Myocardial Hypertrophy in Ovariectomized Mice by Regulating Autophagy
by Shuaishuai Zhang, Jipeng Ma, Xiaowu Wang, Diancai Zhao, Jinglong Zhang, Liqing Jiang, Weixun Duan, Xiaoya Wang, Ziwei Hong, Zilin Li and Jincheng Liu
Int. J. Mol. Sci. 2023, 24(2), 904; https://doi.org/10.3390/ijms24020904 - 4 Jan 2023
Cited by 3 | Viewed by 3128
Abstract
The incidence of heart failure mainly resulting from cardiac hypertrophy and fibrosis increases sharply in post-menopausal women compared with men at the same age, which indicates a cardioprotective role of estrogen. Previous studies in our group have shown that the novel estrogen receptor [...] Read more.
The incidence of heart failure mainly resulting from cardiac hypertrophy and fibrosis increases sharply in post-menopausal women compared with men at the same age, which indicates a cardioprotective role of estrogen. Previous studies in our group have shown that the novel estrogen receptor G Protein Coupled Receptor 30 (GPR30) could attenuate myocardial fibrosis caused by ischemic heart disease. However, the role of GPR30 in myocardial hypertrophy in ovariectomized mice has not been investigated yet. In this study, female mice with bilateral ovariectomy or sham surgery underwent transverse aortic constriction (TAC) surgery. After 8 weeks, mice in the OVX + TAC group exhibited more severe myocardial hypertrophy and fibrosis than mice in the TAC group. G1, the specific agonist of GPR30, could attenuate myocardial hypertrophy and fibrosis of mice in the OVX + TAC group. Furthermore, the expression of LC3II was significantly higher in the OVX + TAC group than in the OVX + TAC + G1 group, which indicates that autophagy might play an important role in this process. An in vitro study showed that G1 alleviated AngiotensionII (AngII)-induced hypertrophy and reduced the autophagy level of H9c2 cells, as revealed by LC3II expression and tandem mRFP-GFP-LC3 fluorescence analysis. Additionally, Western blot results showed that the AKT/mTOR pathway was inhibited in the AngII group, whereas it was restored in the AngII + G1 group. To further verify the mechanism, PI3K inhibitor LY294002 or autophagy activator rapamycin was added in the AngII + G1 group, and the antihypertrophy effect of G1 on H9c2 cells was blocked by LY294002 or rapamycin. In summary, our results demonstrate that G1 can attenuate cardiac hypertrophy and fibrosis and improve the cardiac function of mice in the OVX + TAC group through AKT/mTOR mediated inhibition of autophagy. Thus, this study demonstrates a potential option for the drug treatment of pressure overload-induced cardiac hypertrophy in postmenopausal women. Full article
(This article belongs to the Special Issue Therapeutic Strategy for Pathological Cardiac Hypertrophy)
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