SIRT1 in Cardiometabolic Pathophysiology: A Narrative Review

Sirtuins (SIRTs) are nicotinic adenine dinucleotide (NAD)+-dependent deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes. Recent in vivo and in vitro studies have successfully demonstrated the involvement of SIRT1 in key pathways for the biological function of the cardiovascular system, including cellular metabolism, senescence, oxidative stress, apoptosis and DNA damage. Based on SIRT1 pathophysiology activity, emerging evidence has stimulated a significant evolution in eventually preventing and treating cardiovascular disease (CVDs) by its modulation. SIRT1 is characterized by a protective role against inflammation, vascular aging, arrhythmias and the development of atherosclerotic plaques. Mechanistically, SIRT1 exerts vasculoprotective effects through deacetylation of key transcription factors leading to reduced inflammation, enhanced antioxidant defense, improved endothelial function, and correct vascular remodeling. This review provides a comprehensive overview of SIRT1-controlled molecular signaling pathways in heart pathophysiology, with particular emphasis on atherosclerosis, hypertension, dyslipidemia, atrial fibrillation, cardiac ischemia and ischemic/reperfusion injury. A deeper understanding of the epigenetic mechanisms by which SIRT1 intervenes in signaling pathways responsible for the onset and development of CVDs is important for speeding up the achievement of selective and effective pharmacological modulation of SIRT1 for future applications in the prevention and treatment of CVDs.