Asiatic acid alleviates Ang-II induced cardiac hypertrophy and fibrosis via miR-126/PIK3R2 signaling

Haiyu Li,Junhui Xing,Yongjuan Ruan,Xiaoxu Tian,Zhe Meng

doi:10.1186/s12986-021-00596-7

Haiyu Li, Junhui Xing + Show 3 more

Open Access

https://doi.org/10.1186/s12986-021-00596-7

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Abstract

BackgroundCardiac hypertrophy is an independent risk factor of many cardiovascular diseases. Studies have demonstrated that microRNA-126 (miR-126) was involved in angiogenesis during physiological and pathological process. However, its role in cardiac hypertrophy has not been known clearly. Our previous study demonstrated that asiatic acid (AA) has obvious protective effect on cardiac hypertrophy. Here, this study aimed to discover the regulatory role of miR-126 and its mechanism in cardiac hypertrophy, and to determine whether AA’s anti-hypertrophy effect is partially miR-126 dependent.MethodsMale Sprague Dawley rats were AngII infused via osmotic minipumps for 4 weeks and were treated with AA (20 mg/kg/day) by oral gavage. Cardiac hypertrophy was assessed using the echocardiography and histological analysis. In vitro studies,cardiomyocyte and cardiac fibroblasts (CF) were treted with AngII and AngII plus AA. And, the effect of AA on miR-126 and PI3K/AKT signaling pathway was investigated.ResultsTreatment of rats with AA decreased the ratio of heart weight to tibia length and hypertrophy markers. In vitro exprements demonstrated that AA significantly attenuated AngII-induced cardiac growth and cardiac fibroblast collagen expression. Moreover, our results found downregulation of miR-126 and activation of PI3K/AKT signaling pathway in AngII infusion induced cardiac hypertrophy model. It was also determined that miR-126 targets PIK3R2 directly.ConclusionsAA supplementation upregulated the expression of miR-126 and conferred cardio-protection effect against AngII induced cardiac hypertrophy.

Highlights

Cardiac hypertrophy is an independent risk factor of many cardiovascular diseases
asiatic acid (AA) attenuated AngII‐induced cardiomyocyte growth and cardiac fibroblasts (CFs) collagen expression in vitro To investigate whether AA has a protective role on the development of cardiac hypertrophy, cell surface area and hypertrophic markers were assessed in H9c2 cells treated with AngII
AA promote the expression of miRNA‐126 in the hypertrophic AngII‐infused rats To explore novel mechanisms underlying the anti-hypertrophy effects of AA, we focused on miR-126 which has attracted a lot of attention in angiogenesis

Summary

Introduction

Cardiac hypertrophy is an independent risk factor of many cardiovascular diseases. Studies have demonstrated that microRNA-126 (miR-126) was involved in angiogenesis during physiological and pathological process. MicroRNAs (miRNAs), a kind of small non-coding RNAs containing approximately 22 nt [8], play important roles in almost all of physiology and pathophysiology process, including proliferation, apoptosis as well as fibrosis [9,10,11]. They serve as post-translational regulators and negatively regulate gene expression by binding to their complementary sequence within their target mRNAs 3’ untranslated regions (UTRs), leading to mRNA degradation or blocked translation [12]. Previous studies have reported the PI3K/AKT signaling pathway was involved in the development of cardiac hypertrophy and fibrosis. Previous studies have reported the PI3K/AKT signaling pathway was involved in the development of cardiac hypertrophy and fibrosis. miR-126 can regulate PI3K/AKT signaling pathway by targeting PIK3R2 (PI3K regulatory subunit 2) [19] and affect the proliferation, migration and angiogenesis

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