IMR Press / FBL / Volume 21 / Issue 6 / DOI: 10.2741/4450

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

PDE5 inhibitors protect against post-infarction heart failure

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1 Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
2 Department of Cardiology, Hainan Branch of PLA General Hospital, Sanya, Hainan, 572013, China
Front. Biosci. (Landmark Ed) 2016, 21(6), 1194–1210; https://doi.org/10.2741/4450
Published: 1 June 2016
Abstract

Heart failure (HF) is one of the main causes for cardiovascular morbidity and mortality. This study was designed to examine the effect of PDE-5 inhibition on cardiac geometry, function and apoptosis in post-infarct HF. Our data revealed that treatment of the PDE-5 inhibitor sildenafil, beginning 3 days after left anterior descending coronary artery ligation, attenuated LV remodeling, cardiac dysfunction, cardiomyocyte apoptosis and mitochondrial anomalies including ATP production, mitochondrial respiratory defects, decline of mitochondrial membrane potential (MMP) and compromised mitochondrial ultrastructure. Sildenafil partially ameliorated the downregulation of Sirt3 protein and acetylation of PGC-1α in peri-infarct myocardial regions. In cultured neonatal mouse ventricular myocytes subjected to hypoxia for 24 hrs, sildenafil suppressed apoptosis, promoted ATP production and elevated MMP, along with the increased Sirt3 protein expression and decreased PGC-1α acetylation. Interestingly, knock down of Sirt3 attenuated or nullified sildenafil-offered beneficial effects. Our findings demonstrated that sildenafil exerts its cardioprotective effect against post-infarction injury by improving mitochondrial ultrastructure and function via the Sirt3/PGC-1α pathway. This observation should shed some lights towards application of sildenafil in energy-related cardiovascular diseases.

Keywords
Phosphodiesterase Inhibitors
Mitochondrial Dysfunction
Heart Failure
Remodeling
Sirt3
PGC-1 alpha deacetylation
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