Targeting S100A8/S100A9: A Proteomic Approach to Uncover Therapeutic Avenues in Aortic Dissection

Abstract

SIRT1 is a histone deacetylase that is highly conserved and relies on nicotinamide adenine dinucleotide (NAD+). Numerous pathologic processes, such as cell division, survival, proliferation, autophagy, and oxidative stress, are regulated by it. The heart and cardiomyocytes are shielded against pathology-related stress by therapeutic SIRT1 activation, especially myocardial ischemia/reperfusion (I/R). One crucial metabolic mechanism that helps people survive energy or nutritional shortages, hypoxia, or oxidative stress is autophagy. Autophagy has two sides when it comes to myocardial injury. While excessive autophagy after reperfusion depletes the cellular components and causes autophagic cell death, autophagy activation during the ischemia phase eliminates excess metabolic waste and helps preserve cardiac myocyte survival. Growing studies on I/R have shown that SIRT1 controls myocardial I/R and is implicated in the process of autophagy. SIRT1 controls autophagy by a number of mechanisms, including the deacetylation of LC3, ATGs, and FOXOs. According to recent research, SIRT1-mediated autophagy has distinct functions depending on the degree of myocardial I/R damage. Targeting the mechanism of SIRT1-mediated autophagy at various phases of I/Rinjury may lead to the development of novel small-molecule medicines, miRNA activators, or blockers. For instance, coptisine, curcumin, berberine, and some miRNAs during reperfusion were implicated in controlling the SIRT1-autophagyaxis, exerting a cardioprotective impact, whereas resveratrol, sevoflurane, quercetin, and melatonin were involved in the ischemic stage. To determine treatment approaches for myocardial I/R damage, we discuss here the potential pathways of autophagy regulation by SIRT1 in myocardial I/R injury and the associated molecular pharmacological applications.