Qi Dan Li Xin pill improves chronic heart failure by regulating mTOR/p70S6k-mediated autophagy and inhibiting apoptosis

Binhao Shi,Jingyu Ni,Yuting Huang,Zongpei Xu,Hui Gao,Jing Wei,Zhengcan Zhou,Yili Wang,Guanwei Fan,Lan Li,Jingyuan Mao,Yunsheng Xu,Jingrui Chen

doi:10.1038/s41598-020-63090-9

Abstract

Myocardial remodeling represents a key factor in chronic heart failure (CHF) development, and is characterized by chronic death of cardiomyocytes. Cardiac function changes may be attributed to inflammation, apoptosis and autophagy. This study assessed the effects of Qi Dan Li Xin Pill (QD) on heart function, inflammatory factors, autophagy and apoptosis in cardiac remodeling in CHF rats upon myocardial infarction (MI) induction. Male SD rats underwent a sham procedure or left anterior descending coronary artery (LADCA) ligation, causing MI. Twenty-eight days after modeling, the animals were treated daily with QD, valsartan and saline for 4 weeks. Echocardiography after 4 weeks of drug intervention revealed substantially improved left ventricular remodeling and cardiac function following QD treatment. As demonstrated by decreased IL-1β, IL-6 and TNF-α amounts, this treatment also inhibited the apoptotic process and protected the viability of the myocardium. These outcomes may be attributed to enhanced autophagy in cardiomyocytes, which further reduced pro-inflammatory and pro apoptotic effects. This process may be achieved by QD regulation of the mTOR/P70S6K signaling pathway, suggesting that the traditional Chinese medicine Qi Dan Li Xin pill is effective in heart protective treatment, and is worth further investigation.

Highlights

Heart Failure (HF) represents a complex ailment that mainly results from cardiomyopathy, abnormal cardiac load and arrythmias, including acute heart failure and chronic heart failure (CHF)
Both QD and valsartan significantly reduced cardiac load in rats with CHF, as observed with left ventricular end systolic volume (P < 0.01) (Fig. 2E). These findings demonstrated that QD had similar or even better effects compared with valsartan
In comparison with sham animals, the model group of chronic heart failure rats showed significantly increased Mechanistic target of rapamycin (mTOR) and phosphorylated mTOR (P-mTOR) amounts (Fig. 8B,C; P < 0.01, P < 0.05), which confirmed that mTOR might have an important function in CHF

Summary

Introduction

Heart Failure (HF) represents a complex ailment that mainly results from cardiomyopathy, abnormal cardiac load and arrythmias, including acute heart failure and CHF. Irreversible cardiomyocyte death is the main cause of CHF, structurally and functionally damaging the heart. Two cell death types are known in CHF, including necrosis and apoptosis[3]. Myocardial infarction (MI)-induced chronic heart failure features substantial systemic and local inflammatory reactions[4]. Myocardial apoptosis is well-documented in the progression of chronic heart failure[7]. The optimal autophagic level is critical to cardiac function maintenance. It was demonstrated autophagy occurring in cardiac myocytes under ischemia can supply needed energy for the survival of cells via removal of disabled organelles or aging proteins[9,10]. Our findings provide novel insights into the mechanisms underpinning QD’s effects in CHF treatment

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Results

Conclusion