The protective role of SIRT1 in cardiovascular disease: from molecular mechanisms to potential therapeutic strategies.

INTRODUCTION

Cardiovascular diseases (CVDs) pose a significant threat to the health of middle-aged and elderly people. They are widely recognized as a major public health concern. The sirtuin (SIRT) family comprises seven proteins (SIRT1-SIRT7), all of which contain a highly conserved nicotinamide adenine dinucleotide (NAD+)-binding catalytic domain. Notably, SIRT1 influences the development and progression of CVDs by regulating biological processes such as inflammation, immune responses, oxidative stress, and autophagy.

AREAS COVERED: This review summarizes the biological functions of SIRT1 and its role in major cardiovascular conditions, with particular attention to cell-type-specific effects. It examines the preclinical efficacy of SIRT1 activators, such as resveratrol and SRT1720, and discusses challenges including dose dependency, specificity, and barriers to clinical translation. A comprehensive literature search (PubMed, Web of Science, Scopus; 2000-April 2026) was conducted to identify studies on SIRT1 in CVDs, with a focus on mechanistic insights and therapeutic relevance.

EXPERT OPINION: We believe that developing highly specific SIRT1 activators, identifying predictive biomarkers, and elucidating tissue-selective regulatory mechanisms can amplify SIRT1's protective effects in cardiac diseases. Current and future clinical trials should establish the safety and efficacy of SIRT1-targeted therapies at the earliest possible stage.