Rutaecarpine Ameliorates Pressure Overload Cardiac Hypertrophy by Suppression of Calcineurin and Angiotensin II

Shujun Li,Jingshan Shi,Qin Wu,Qingsong Jiang,Changfei Zhou,Bo Huang,Lixin Wei

doi:10.1155/2021/8857329

Abstract

Cardiac hypertrophy is a major pathological process to result in heart failure and sudden death. Rutaecarpine, a pentacyclic indolopyridoquinazolinone alkaloid extracted from Evodia rutaecarpa with multiple pharmacological activities, yet the underlying protective effects and the mechanisms on cardiac hypertrophy remain unclear. This study aimed to evaluate the potential effects of rutaecarpine on pressure overload cardiac hypertrophy. Cardiac hypertrophy in rat was developed by abdominal aortic constriction (AAC) for 4 weeks, which was improved by rutaecarpine supplementation (20 or 40 mg/kg/day, i.g.) for another 4 weeks. The level of angiotensin II was increased; the mRNA expression and the activity of calcineurin in the left ventricular tissue were augmented following cardiac hypertrophy. Rutaecarpine administration decreased angiotensin II content and reduced calcineurin expression and activity. Noteworthily, in angiotensin II-induced cardiomyocytes, rutaecarpine ameliorated the hypertrophic effects in a dose-dependent manner and downregulated the increased mRNA expression and activity of calcineurin. In conclusion, rutaecarpine can improve cardiac hypertrophy in pressure overload rats, which may be related to the inhibition of angiotensin II-calcineurin signal pathway.

Highlights

Cardiac hypertrophy is considered as a compensatory response to maintain cardiac output during various physiological and pathological conditions
(LV + S)/ Body weight (BW), (LV + S)/right ventricle (RV), and atrial natriuretic factor (ANF) mRNA expression significantly increased in model group (P < 0.05), in comparison with sham-operated group. e pathomorphology of the left ventricle showed that larger cardiomyocytes and irregular and disruptive fiber in model group were observed
In the response to long-standing arterial hypertension, heart function is maintained through enlarged cardiomyocytes and increased protein synthesis, accompanied by the reactivation of the fetal gene expression, such as ANF, which are the characteristics of cardiac hypertrophy. e abdominal aorta is constricted to increase cardiac pressure overload and induce cardiac hypertrophy, which is more clinically relevant and similar to the human form of the disease [9, 14]

Summary

Introduction

Cardiac hypertrophy is considered as a compensatory response to maintain cardiac output during various physiological and pathological conditions. Prolonged hypertrophy often leads to decompensation, resulting in heart failure and sudden death. Many factors including mechanical stress and neurohumoral stimulation induce cardiac hypertrophy [1]. Angiotensin II has been identified as one of the most powerful stimuli in inducing cardiac hypertrophy. It has been reported that angiotensin II-activated Ca2+ signaling pathway initiated the progress of cardiomyocytes hypertrophy. Angiotensin II activates G protein-dependent signaling pathways in cardiomyocytes that evokes Ca2+ entry [2]. E sustained intracellular Ca2+ concentration ([Ca2+]i) increase induces pathological myocardial hypertrophy through activation of Ca2+-dependent signaling pathway such as Ca2+-calcineurin, which directly participates in several extracellular signal pathways causing myocardial hypertrophy Angiotensin II activates G protein-dependent signaling pathways in cardiomyocytes that evokes Ca2+ entry [2]. e sustained intracellular Ca2+ concentration ([Ca2+]i) increase induces pathological myocardial hypertrophy through activation of Ca2+-dependent signaling pathway such as Ca2+-calcineurin, which directly participates in several extracellular signal pathways causing myocardial hypertrophy

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Results

Conclusion