Roles of Sirtuins in Cardiovascular Diseases: Mechanisms and Therapeutics

Cardiovascular diseases (CVDs) are experiencing a rapid surge and are widely recognized as the leading cause of mortality in the current aging society. Given the multifactorial etiology of CVDs, understanding the intricate molecular and cellular mechanisms is imperative. Over the past 2 decades, many scientists have focused on Sirtuins, a family of nicotinamide adenine dinucleotide-dependent deacylases. Sirtuins are highly conserved across species, from yeasts to primates, and play a crucial role in linking aging and diseases. Sirtuins participate in nearly all key physiological and pathological processes, ranging from embryogenic development to stress response and aging. Abnormal expression and activity of Sirtuins exist in many aging-related diseases, while their activation has shown efficacy in mitigating these diseases (eg, CVDs). In terms of research, this field has maintained fast, sustained growth in recent years, from fundamental studies to clinical trials. In this review, we present a comprehensive, up-to-date discussion on the biological functions of Sirtuins and their roles in regulating cardiovascular biology and CVDs. Furthermore, we highlight the latest advancements in utilizing Sirtuin-activating compounds and nicotinamide adenine dinucleotide boosters as potential pharmacological targets for preventing and treating CVDs. The key unresolved issues in the field-from the chemicobiological regulation of Sirtuins to Sirtuin-targeted CVD investigations-are also discussed. This timely review could be critical in understanding the updated knowledge of Sirtuin biology in CVDs and facilitating the clinical accessibility of Sirtuin-targeting interventions.