Cellular and molecular biology of sirtuins in cardiovascular disease

Abstract

Sirtuins (SIRTs) are a nicotinic adenine dinucleotide (+) -dependent histone deacetylase that regulates critical signaling pathways in prokaryotes and eukaryotes. Studies have identified seven mammalian homologs of the yeast SIRT silencing message regulator 2, namely, SIRT1-SIRT7. Recent in vivo and in vitro studies have successfully demonstrated the involvement of SIRTs in key pathways for cell biological function in physiological and pathological processes of the cardiovascular system, including processes including cellular senescence, oxidative stress, apoptosis, DNA damage, and cellular metabolism. Emerging evidence has stimulated a significant evolution in preventing and treating cardiovascular disease (CVD). Here, we review the important roles of SIRTs for the regulatory pathways involved in the pathogenesis of cardiovascular diseases and their molecular targets, including novel protein post-translational modifications of succinylation. In addition, we summarize the agonists and inhibitors currently identified to target novel specific small molecules of SIRTs. A better understanding of the role of SIRTs in the biology of CVD opens new avenues for therapeutic intervention with great potential for preventing and treating CVD.

Keywords

• Sirtuin
• Drug discovery
• Myocardial hypertrophy
• Heart failure
• Ischemic reperfusion
• Atherosclerosis