Semaphorin‑3A alleviates cardiac hypertrophy by regulating autophagy

Sun,Yu; Dong,Jin; Chai,Xiaohong; Wang,Jingping; Li,Bao; Yang,Jinjing

doi:10.3892/etm.2023.12326

Semaphorin‑3A alleviates cardiac hypertrophy by regulating autophagy

Authors:
- Yu Sun
- Jin Dong
- Xiaohong Chai
- Jingping Wang
- Bao Li
- Jinjing Yang
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Affiliations: Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Cardiology, Shanxi Province Cardiovascular Hospital, Taiyuan, Shanxi 030024, P.R. China
Published online on: November 28, 2023 https://doi.org/10.3892/etm.2023.12326
Article Number: 38
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cardiac hypertrophy, characterized by cardiomyocyte enlargement, is an adaptive response of the heart to certain hypertrophic stimuli; however, prolonged hypertrophy results in cardiac dysfunction and can ultimately cause heart failure. The present study evaluated the role of semaphorin‑3A (Sema3A), a neurochemical inhibitor, in cardiac hypertrophy, utilizing an isoproterenol (ISO) induced H9c2 cell model. Cells were stained with rhodamine‑phalloidin to assess the cell surface area and reverse transcription‑quantitative PCR was performed to quantify mRNA expression levels of Sema3A, brain natriuretic factor (BNF) and β‑myosin heavy chain (β‑MHC). The protein expression levels of the autophagy‑related proteins light chain 3 (LC3), p62 and Beclin‑1, and the Akt/mTOR signaling pathway associated proteins Akt, phosphorylated (p)‑Akt, mTOR, p‑mTOR, 4E‑binding protein 1 (4EBP1) and p‑4EBP1 were semi‑quantified using western blotting. Rapamycin, a canonical autophagy inducer, was administered to H9c2 cells to elucidate the regulatory mechanism of Sema3A. The results indicated significantly increased cell surface area and elevated BNF and β‑MHC mRNA expression levels, increased LC3II/I ratio and Beclin‑1 protein expression levels and significantly decreased p62 protein expression levels after treatment of H9c2 cardiomyocytes with ISO for 24 h. Sema3A overexpression improved ISO‑induced hypertrophy in H9c2 cells, indicated by decreased cell surface area and reduced BNF and β‑MHC mRNA expression levels. Moreover, Sema3A overexpression inhibited ISO‑induced autophagy in H9c2 cells, indicated by decreased LC3II/I ratio and Beclin‑1 protein expression levels and increased p62 protein expression levels. The autophagy activator rapamycin partially inhibited the protective effect of Sema3A on ISO‑induced hypertrophy. Sema3A overexpression suppressed the decrease of the protein expression levels of p‑Akt, mTOR and their downstream target 4EBP1, which is induced by ISO. Collectively, these results suggested Sema3A prevented ISO‑induced cardiac hypertrophy by inhibiting autophagy via the Akt/mTOR signaling pathway.

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