SUMOylation as a Therapeutic Target for Myocardial Infarction

Abstract

Myocardial infarction is a prevalent and life-threatening cardiovascular disease. The main goal of existing interventional therapies is to restore coronary reperfusion while few are designed to ameliorate the pathology of heart diseases via targeting the post-translational modifications of those critical proteins. Small ubiquitin-like modifier (SUMO) proteins are recently discovered to form a new type of protein post-translational modifications (PTM), known as SUMOylation. SUMOylation and deSUMOylation are dynamically balanced in the maintenance of various biological processes including cell division, DNA repair, epigenetic transcriptional regulation, and cellular metabolism. Importantly, SUMOylation plays a critical role in the regulation of cardiac functions and the pathology of cardiovascular diseases, especially in heart failure and myocardial infarction. This review summarizes the current understanding on the effects of SUMOylation and SUMOylated proteins in the pathophysiology of myocardial infarction and identifies the potential treatments against myocardial injury via targeting SUMO. Ultimately, this review recommends SUMOylation as a key therapeutic target for treating cardiovascular diseases.

SUMOylation of Nuclear γ-Actin by SUMO2 supports DNA Damage Repair against Myocardial Ischemia-Reperfusion Injury

“…SUMOylation of proteins has emerged as an important therapeutic target for drug discovery 8 , 14 . We recently demonstrated that natural product puerarin protected cardiomyocytes against ischemia reperfusion injury via up-regulating SUMO2 and SUMOylation without altering SUMO1 expression 8 . The present study was designed to identify SUMO2-modified proteins and elucidate the cardioprotective mechanisms.…”

“…Timely intitiation of DNA repair is crucial to maintain genome integrity and enhance survival 58 . On the other hand, we recently proposed that SUMO2 might exhibit cardioprotective activity via increasing SUMOylation of specific proteins in myocardial infarction 8 . In the present study, firstly, we validated that the discrepancy in the intracellular localization of SUMO2 and γ-actin and the status of DNA damage in a mouse model of myocardial infarction and H9c2 cell model of hypoxia reoxygenation.…”

“…Interestingly, oxidative DNA damage may be attenuated by antioxidants, nicotinamide adenine dinucleotide (NAD + ) boosters and enzymes involved in oxidative DNA repair processes 5 . Nevertheless, the proteins that regulate cardiac functions and DNA damage repair are tightly regulated by post-translational modifications (PTMs) including acetylation, methylation, ubiquitinylation and sumoylation 7 , 8 . Thus, PTMs may be an important tagert for the therapy of myocardial infarction.…”

Natural Products Against Renal Fibrosis via Modulation of SUMOylation

“…Meanwhile, astragaloside IV promotes the proliferation and migration of vascular endothelial cells and antagonizes the adverse microenvironment of hypoxia and high glucose by enhancing SUMO1 expression in human umbilical vein endothelial cells (Wang B. S. et al, 2021). In cardiomyocytes, puerarin attenuates cellular inflammatory response and fibrosis through activating ER/ERK pathway by increasing the expression of SUMO2 (Zhao et al, 2021a). In oral squamous cell carcinoma cells, ginkgolic acid suppresses tumorigenicity and tumor progression through inhibition of the enhancement of SUMOylation of Smad4 (Liu et al, 2020).…”

Baicalin regulates stem cells as a creative point in the treatment of climacteric syndrome

“…Myocardial infarction is a common cardiovascular disease of rapid onset ( Zhao et al, 2021 ). Current evidence suggests that although reperfusion can reduce cardiac tissue injury, it increases perfusion injury ( Zhang G. et al, 2021 ).…”