Effects of Total Flavone from Rhododendron simsii Planch. Flower on Postischemic Cardiac Dysfunction and Cardiac Remodeling in Rats.

Xinqi Cheng,Jie Zhang,Zhiwu Chen

doi:10.1155/2017/5389272

Abstract

This study investigated the effect of total flavone from Rhododendron simsii Planch. flower (TFR) on postischemic cardiac dysfunction and ventricular remodeling and was to test the hypothesis that TFR has an antiventricular remodeling effect through inhibition of urotensin-II receptor- (UTR-) mediated activation of RhoA-ROCK pathways. Twenty-four hours after ligation of the left anterior descending coronary artery, male Sprague-Dawley rats were randomized to receive 4-week treatment with saline (model group) or TFR. Compared to the model group, TFR treatment restored cardiac function, attenuated cardiomyocyte hypertrophy, and reduced interstitial fibrosis. Expression levels of several fibrosis-related factors, including alpha-smooth muscle actin, transforming growth factor-beta 1, matrix metalloproteinase-2, and collagen type I, were increased after MI. TFR treatment attenuated the upregulation of these factors, downregulated UTR expression, and markedly diminished the expression of RhoA and ROCK1/2. These results suggested that TFR could improve cardiac function and ameliorate ventricular remodeling through blocking UTR-mediated activation of RhoA-ROCK pathways in myocardial infarction rats.

Highlights

Progressive cardiac remodeling, which may include myocyte hypertrophy, interstitial fibrosis, and ventricular dilation [1, 2] after myocardial infarction (MI), is a leading cause of morbidity and mortality worldwide
Ventricular remodeling after acute MI results from infarct expansion followed by hypertrophy
A MI-induced ventricular remodeling model was established in rats, and this model exhibits left ventricular (LV) enlargement, cardiac dysfunction, and high mortality rates up to 4 weeks after MI

Summary

Introduction

Progressive cardiac remodeling, which may include myocyte hypertrophy, interstitial fibrosis, and ventricular dilation [1, 2] after myocardial infarction (MI), is a leading cause of morbidity and mortality worldwide. The RhoAROCK pathway plays an important role and is a novel therapeutic target for cardiovascular diseases [11]. Activation of the RhoA/ROCK pathway can induce activation of hypertrophy-related genes [12, 13]. Several studies have demonstrated a relationship between U-II/UTR and the RhoA-ROCK pathway in the migration of vascular smooth muscle cells and acute myocardial injury [15, 16]. Our recent study demonstrated that inhibition of the UTR-RhoA-ROCK pathway exerts a potent protective effect on MI in rats [16]. The role of the UTR-RhoA-ROCK pathway in cardiac remodeling has not been determined

Methods

Results

Conclusion