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

Abstract

Mitochondrial biosynthesis regulated by the PGC-1a-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 apoptosis of myocardial cells. Notably, PER remarkably up-regulated the mRNA and protein expression levels of Sirtuin 3 (SIRT3), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM) in myocardial cells. Collectively, our results suggest that PER induces mitochondrial biosynthesismediated enhancement of SIRT3 and PGC-1a expression, thereby improving the cardiac function in rats with ISO-induced cardiomyopathy.

RETRACTED: MicroRNA-410-3p Binds to TLR2 and Alleviates Myocardial Mitochondrial Dysfunction and Chemokine Production in LPS-Induced Sepsis

“…A previous study noted that increased ATP production in myocardial tissues was correlated with improved functioning of the mitochondrial respiratory chain. 18 Similarly, amplified secretion of chemokine has also been was observed at the site of infection in polymicrobial sepsis, while TLR2 silencing brought about a decrease in chemokine production in our findings. 19 Interestingly, a previously conducted report has indicated that LPS treatment at certain doses brings about marked elevations in the expression of TLR2 at both mRNA and protein levels in rat kidney epithelial cells.…”

Trimetazidine Ameliorates Myocardial Metabolic Remodeling in Isoproterenol-Induced Rats Through Regulating Ketone Body Metabolism via Activating AMPK and PPAR α

“…Meanwhile, the ISO-induced HF group was given a subcutaneous injection of ISO (Purity 98%) at 10 mg/kg/d. The infusion was consecutive in the preceding two weeks (Zhu et al, 2020). Afterward, the survived rats in the ISO-induced HF group were further randomly divided into ISO (n = 10) and ISO +TMZ group (n =10).…”

Perindopril/Ambrosin Combination Mitigates Dextran Sulfate Sodium-Induced Colitis in Mice: Crosstalk between Toll-Like Receptor 4, the Pro-Inflammatory Pathways, and SIRT1/PPAR-γ Signaling

“…In the present study, perindopril administration to DSS-treated mice was associated with a significant increase in the levels of Nrf2 and the antioxidant enzymes, together with a significant decrement in iNOS and ROS levels when compared to mice treated with DSS alone. This may be explained by the findings of Zhu et al [ 32 ], who reported that among other ACE inhibitors, perindopril exerts outstanding antioxidant effects in various body tissues. Ancion et al [ 33 ] attributed the antioxidant effects of perindopril to its ability to decrease angiotensin II levels, thereby reducing ROS production.…”