Can Sirtuin 1 Serve as a Therapeutic Target in Pulmonary Arterial Hypertension? A Comprehensive Review

Pulmonary arterial hypertension (PAH) is a progressive, currently incurable disease characterized by elevated pulmonary arterial pressure, vascular remodeling, and right ventricular hypertrophy, eventually leading to heart failure and death. Sirtuin 1 (SIRT1), a NAD⁺-dependent deacetylase, regulates endothelial and vascular smooth muscle function, and its activation by compounds such as resveratrol or SRT1720 shows therapeutic potential by reducing pulmonary and right ventricular pressures and limiting vascular remodeling in both preventive and therapeutic experimental models, highlighting their potential translational relevance. To date, no comprehensive review has focused on the role of SIRT1 in PAH. This review summarizes the molecular mechanisms of SIRT1 action in the cardiopulmonary system and discusses its therapeutic potential in PAH treatment.