Gallic acid improves cardiac dysfunction and fibrosis in pressure overload-induced heart failure

Li Jin,Bin Liu,Zhe Hao Piao,Gwi Ran Kim,Sin Young Choi,Hae Jin Kee,Myung Ho Jeong,Simei Sun,Yuhee Ryu,Hyung-Seok Kim

doi:10.1038/s41598-018-27599-4

Abstract

Gallic acid is a trihydroxybenzoic acid found in tea leaves and some plants. Here, we report the effect of gallic acid on cardiac dysfunction and fibrosis in a mouse model of pressure overload-induced heart failure and in primary rat cardiac fibroblasts, and compare the effects of gallic acid with those of drugs used in clinics. Gallic acid reduces cardiac hypertrophy, dysfunction, and fibrosis induced by transverse aortic constriction (TAC) stimuli in vivo and transforming growth factor β1 (TGF-β1) in vitro. It decreases left ventricular end-diastolic and end-systolic diameter, and recovers the reduced fractional shortening in TAC. In addition, it suppresses the expression of atrial natriuretic peptide, brain natriuretic peptide, skeletal α-actin, and β-myosin heavy chain. Administration of gallic acid decreases perivascular fibrosis, as determined by Trichrome II Blue staining, and reduces the expression of collagen type I and connective tissue growth factor. However, administration of losartan, carvedilol, and furosemide does not reduce cardiac dysfunction and fibrosis in TAC. Moreover, treatment with gallic acid inhibits fibrosis-related genes and deposition of collagen type I in TGF-β1-treated cardiac fibroblasts. These results suggest that gallic acid is a therapeutic agent for cardiac dysfunction and fibrosis in chronic heart failure.

Highlights

Heart failure is a major health concern worldwide, and it is a leading cause of morbidity and mortality in the United States and in other developed countries
Our findings demonstrate that gallic acid can be a novel therapeutic agent to treat cardiac dysfunction and fibrosis in heart failure
The present study demonstrates that gallic acid improves cardiac dysfunction and fibrosis in a mouse model of pressure overload-induced heart failure and in primary rat cardiac fibroblasts

Summary

Introduction

Heart failure is a major health concern worldwide, and it is a leading cause of morbidity and mortality in the United States and in other developed countries. There are several animal heart failure models, including that of transverse aortic constriction (TAC), left anterior descending ligation, and the aged spontaneously hypertensive rat. TAC mimics human aortic stenosis, and it induces cardiac hypertrophy and heart failure in animals[2]. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers (ARBs), and beta-blockers are clinically used to treat heart failure. Improving or treating heart failure, the 5-year mortality rate of this condition ranges from 45% to 60%9. We investigated the effect of gallic acid in a mouse model of TAC-induced heart failure and in cultured rat fibroblast cells. Our findings demonstrate that gallic acid can be a novel therapeutic agent to treat cardiac dysfunction and fibrosis in heart failure

Methods

Results

Conclusion