Cardiomyocyte-specific knockout of endothelin receptor a attenuates obesity cardiomyopathy

Biochimica Et Biophysica Acta. Molecular Basis of Disease
Asli F CeylanJun Ren

Abstract

Endothelin (ET)-1 is implicated in the pathophysiology of cardiovascular diseases although its role in obesity anomalies has not been fully elucidated. This study was designed to examine the impact of ET-1 receptor A (ETA) ablation on obesity-induced changes in cardiac geometry and contractile function, as well as the mechanisms involved with a focus on autophagy. Cardiomyocyte-specific ETA receptor knockout (ETAKO) and WT mice were fed either low-fat (10% calorie from fat) or high-fat (45% calorie from fat) diet for 24 weeks. Glucose tolerance test was examined to confirm insulin resistance. High-fat diet intake compromised myocardial geometry (enlarged left ventricular diameters in systole and diastole), morphology (cardiac hypertrophy, increased wall thickness and interstitial fibrosis), contractile function (reduced fractional shortening, ejection fraction and cardiomyocyte shortening) and intracellular Ca2+ handling, the effect of which was significantly attenuated by ETAKO. TUNEL staining revealed overt apoptosis in high-fat-fed group, the effect was reverted by ETAKO. Western blot analysis noted that high-fat intake downregulated leptin receptor and PPARγ, insulin signaling (elevated basal/dampened insulin-stimulated pho...Continue Reading

Citations

Sep 29, 2020·Frontiers in Physiology·Lingfei LiJiongyu Hu
Jun 9, 2020·Frontiers in Endocrinology·Xiaoqiang TangHou-Zao Chen
Jun 2, 2020·Frontiers in Pharmacology·Arpad Tosaki
Aug 3, 2019·Canadian Journal of Physiology and Pharmacology·Xavier Lieben LouisThomas Netticadan
Oct 7, 2020·Pharmacology & Therapeutics·Qirong LuMaría-Aránzazu Martínez
May 6, 2021·Physiological Reviews·Jun RenYingmei Zhang

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