Ginkgolide B Protects Cardiomyocytes from Angiotensin II-Induced Hypertrophy via Regulation of Autophagy through SIRT1-FoxO1.

Qingyuan Jiang,Jinyu Li,Zhongsheng Zhu,Ming Lu,Victor Garcia

doi:10.1155/2021/5554569

Qingyuan Jiang, Jinyu Li + Show 3 more

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https://doi.org/10.1155/2021/5554569

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Journal: Cardiovascular Therapeutics	Publication Date: Jun 23, 2021
Citations: 9	License type: CC BY 4.0

Affiliation: Pudong Medical Center

Abstract

Ginkgolide B (GB) is an active ingredient extracted from Ginkgo biloba leaves. However, the effects of GB on cardiac hypertrophy remain unclear. The study is aimed at determining whether GB could alleviate cardiac hypertrophy and exploring its underlying molecular mechanism. Rat cardiomyocyte cell line H9c2 cells were pretreated with GB and incubated with angiotensin II (Ang II) to simulate an in vitro cardiac hypertrophy model. Cell viability, cell size, hypertrophy markers, and autophagy were determined in H9c2 cells after Ang II treatment. Proteins involved in autophagy and the SIRT1 pathway were determined by western blot. Our data demonstrated that GB attenuated Ang II-induced cardiac hypertrophy and reduced the mRNA expressions of hypertrophy marker, atrial natriuretic peptide (ANP), and β-myosin heavy chain (β-MHC). GB further increased Ang II-induced autophagy in H9c2 cells and modulated expressions of autophagy-related proteins Beclin1 and P62. Modulation of autophagy using autophagy inhibitor 3-methyladenine (3-MA) could abrogate GB-downregulated transcription of NPPA. We then showed that GB attenuated Ang II-induced oxidative stress and reduction in SIRT1 and FoxO1 protein expression. Finally, the effect of GB on autophagy and cardiac hypertrophy could be reversed by SIRT1 inhibitor EX-527. GB inhibits Ang II-induced cardiac hypertrophy by enhancing autophagy via the SIRT1-FoxO1 signaling pathway and might be a potential agent in treating pathological cardiac hypertrophy.

Highlights

Cardiac hypertrophy is a compensatory response after injury, and its main pathological feathers are enlargement of myocardial cell size and increase of protein synthesis, including physiological hypertrophy and pathological hypertrophy [1]
H9c2 cells were incubated with Ang Angiotensin II atrial natriuretic peptide (ANP) (II) at various concentrations for 48 h, and the hypertrophy markers were detected
It showed that Angiotensin II (Ang II) markedly increased cardiomyocyte size of H9c2 cells, and this change was suppressed by Ginkgolide B (GB) (Figures 1(d) and 1(e))

Summary

Introduction

Cardiac hypertrophy is a compensatory response after injury, and its main pathological feathers are enlargement of myocardial cell size and increase of protein synthesis, including physiological hypertrophy and pathological hypertrophy [1]. Physiological hypertrophy is benign, mainly referring to compensatory and adaptive changes of the heart to external stimuli such as physical exercise, without pathological characteristics [2]. Pathological hypertrophy is harmful, causes apoptosis and necrosis of myocardial cells, increases cardiac fibroblasts, and makes the functional cardiomyocytes be replaced by fibrous connective tissue [3]. Previous studies have shown that persistent pathological hypertrophy is a key progressive factor and predictive marker of heart failure [4]. To directly affect hemodynamics, Ang II is a critical cell growth factor, which can induce cardiomyocyte hypertrophy, promote cardiac fibroblast proliferation, and induce cardiomyocyte apoptosis [7, 8]. Ang II is an essential stimulating factor for cardiovascular diseases with hypertrophy, such as hypertension and heart failure [9]

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