Perindopril Improves Cardiac Function by Enhancing the Expression of SIRT3 and PGC-1α in a Rat Model of Isoproterenol-Induced Cardiomyopathy

Frontiers in Pharmacology
Zhenyu ZhuXin Qi

Abstract

Mitochondrial biosynthesis regulated by the PGC-1α-NRF1-TFAM pathway is considered a novel potential therapeutic target to treat heart failure (HF). Perindopril (PER) is an angiotensin-converting enzyme inhibitor that has proven efficacy in the prevention of HF; however, its mechanism is not well established. In this study, to investigate the mechanisms of PER in cardiac protection, a rat model of cardiomyopathy was established by continuous isoproterenol (ISO) stimulation. Changes in the body weight, heart weight index, echocardiography, histological staining, mitochondrial microstructure, and biochemical indicators were examined. Our results demonstrate that PER reduced myocardial remodeling, inhibited deterioration of cardiac function, and delayed HF onset in rats with ISO-induced cardiomyopathy. PER markedly reduced reactive oxygen species (ROS) production, increased the levels of antioxidant enzymes, inhibited mitochondrial structural destruction and increases the number of mitochondria, improved the function of the mitochondrial respiratory chain, and promoted ATP production in myocardial tissues. In addition, PER inhibited cytochrome C release in mitochondria and caspase-3 activation in the cytosol, thereby reducing the ...Continue Reading

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Citations

Aug 18, 2020·Inflammation·Ugur KostakogluHuseyin Avni Uydu
Jul 10, 2021·Oxidative Medicine and Cellular Longevity·Judith Bernal-RamírezGerardo García-Rivas
Aug 8, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Chunfang WangLi Shen

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Methods Mentioned

BETA
light microscopy
ELISA
Assay
flow cytometry
PCR
protein assay
electrophoresis
MDA

Software Mentioned

Image J
SPSS

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