Canagliflozin Ameliorates Ventricular Remodeling through Apelin/Angiotensin-Converting Enzyme 2 Signaling in Heart Failure with Preserved Ejection Fraction Rats

内科学 厄贝沙坦 医学 心室重构 射血分数 心脏病学 心力衰竭 心肌纤维化 阿佩林 血管紧张素转化酶2 血压 舒张期 纤维化 血管紧张素II 左心室肥大 心功能曲线 心脏纤维化 内分泌学 受体 疾病 2019年冠状病毒病(COVID-19) 传染病(医学专业)
作者
Tingting Zhang,Xinyu Wang,Zhongli Wang,Jianlong Zhai,Lili He,Yan Wang,Qingjuan Zuo,Sai Ma,Guorui Zhang,Yifang Guo
出处
期刊:Pharmacology [S. Karger AG]
卷期号:108 (5): 478-491 被引量:4
标识
DOI:10.1159/000533277
摘要

The aim of this study was to investigate the effect of canagliflozin (CANA) on ventricular remodeling in patients with preserved ejection fraction (HFpEF) heart failure and to further investigate its possible molecular mechanisms.A high-salt diet was used to induce the formation of HFpEF model in salt-sensitive rats. The rats were fed with CANA and irbesartan, respectively. The mice were divided into control group, model group, CANA group, irbesartan group, and combined drug group. After 12 weeks of feeding, the rats were evaluated by measuring the relevant indexes and echocardiography for cardiac function. Histological analysis was performed using Masson trichrome staining and immunohistochemical staining. RT-qPCR and Western blot were used to quantify the relevant genes and proteins.In this study, CANA exhibited diuresis, decreased blood pressure, weight loss, and increased food and water intake. Following a high-salt diet, Dahl salt-sensitive rats developed hypertension followed by left ventricular diastolic dysfunction, myocardial fibrosis, and left ventricular remodeling. Myocardial hypertrophy and fibrosis were reduced, and left ventricular diastolic function and ventricular remodeling improved after CANA treatment. The combination of CANA and irbesartan was superior to monotherapy in reducing blood pressure and improving cardiac insufficiency and left ventricular diastolic dysfunction in rats. CANA improves myocardial fibrosis, left ventricular diastolic dysfunction, and ventricular remodeling by upregulating apelin, activating angiotensin-converting enzyme 2 (ACE2), and increasing ACE2/Ang (1-7)/MASR axis levels.CANA improves myocardial fibrosis, left ventricular diastolic dysfunction, and ventricular remodeling in HFpEF rats through upregulation of apelin/ACE2 signaling.
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