Perindopril and a Galectin-3 Inhibitor Improve Ischemic Heart Failure in Rabbits by Reducing Gal-3 Expression and Myocardial Fibrosis.

Sha Li,Wenhao Deng,Yuehua Zhang,Xiao Hao,Shuren Li

doi:10.3389/fphys.2019.00267

Abstract

Objective: Ventricular remodeling is considered the basis of heart failure and is involved in myocardial fibrosis. This study aimed to assess perindopril and a galectin-3 inhibitor (modified citrus pectin, MCP) for their effects on ventricular remodeling and myocardial fibrosis in rabbits with ischemic heart failure.Methods: Rabbits were divided into sham, heart failure (model), MCP, and perindopril groups, respectively. A rabbit model of ischemic heart failure was established by ligating the anterior descending coronary artery. Then, the rabbits were orally administered MCP, perindopril, or saline (all at 2 ml/kg/d) for 4 weeks. Sham animals only underwent open heart surgery without further treatment. After 4 weeks, cardiac function was examined by ultrasound, and myocardial Gal-3, collagen type I, and collagen type III expression was assessed, at the gene and protein levels, by real-time PCR and Western-Blot, respectively; serum Gal-3 was detected by ELISA, and fibrosis in the infarct zone was evaluated by H&E and Masson staining.Results: In model animals, myocardial Gal-3, collagen type I, and collagen type III gene and protein expression levels were increased compared with control values, as well as serum Gal-3 amounts. Treatment with perindopril and MCP significantly alleviated the above effects, with no significant differences between the treatment groups. Pathological analyses showed that compared with model animals, treatment with MCP or perindopril resulted in relatively neatly arranged myocardial cells in the infarct zone, with significantly decreased fibrosis.Conclusion: Perindopril and the galectin-3 inhibitor MCP comparably improve ischemic heart failure in rabbits, by downregulating Gal-3 and reducing myocardial fibrosis.

Highlights

After Myocardial Infarction (MI), a large number of myocardial cell necrosis, hyperplasia of fibrous tissue, scar formation, as the consequent process to cardiac the adaptive dynamic the processes to the as cardiac apoptosis, angiogenesis, fibrosis, and hypertrophy and ventricular remodeling and cardiac function decline, often appear in late refractory heart failure (Marfella et al, 2013a; Galectin-3 Inhibitor Improve Heart FailureSardu et al, 2014, 2016)
In the MCP group, 9 animals survived and 1 died of pneumothorax; 8 rabbits survived in the perindopril group, while one each died of pneumothorax during chest opening and ventricular fibrillation induced by the ligation of the anterior descending coronary artery
Two weeks after the surgical operation, left ventricular ejection fraction (LVEF) and left ventricular end diastolic diameter (LVEDD) significantly differed among groups, with increased LVEF and reduced LVEDD in animals with heart failure compared with the sham group

Summary

Introduction

After Myocardial Infarction (MI), a large number of myocardial cell necrosis, hyperplasia of fibrous tissue, scar formation, as the consequent process to cardiac the adaptive dynamic the processes to the as cardiac apoptosis, angiogenesis, fibrosis, and hypertrophy and ventricular remodeling and cardiac function decline, often appear in late refractory heart failure (Marfella et al, 2013a; Galectin-3 Inhibitor Improve Heart FailureSardu et al, 2014, 2016). Ventricular remodeling is considered the basis for the development of heart failure (Kalyanasundaram et al, 2013). Myocardial fibrosis plays an important role in the incidence and development of ventricular remodeling and heart failure (Chen et al, 2012; Psarras et al, 2012). In recent years, delaying the progression of ventricular remodeling has become the main direction for heart failure treatment (Yancy et al, 2017). The associations of Galectin-3 (Gal-3) with heart failure and ventricular remodeling attract increasing attention (Amin et al, 2017; Baggen et al, 2017; van Vark et al, 2017). Based on the above, inhibiting Gal-3 could become a new direction in the treatment of heart failure

Methods

Results

Discussion

Conclusion