Sirtuin-3-Mediated Cellular Metabolism Links Cardiovascular Remodeling with Hypertension

SIMPLE SUMMARY: Sirtuin-3 (SIRT3) performs a vital role in regulating metabolism, mitochondrial function, and oxidative stress. It has been connected to cardiovascular diseases, including hypertension. Studies indicate that hypertensive patients have reduced SIRT3 expression, leading to an upsurge in reactive oxygen species (ROS) levels and mitochondrial dysfunction. By deacetylating and activating antioxidants, SIRT3 helps regulate ROS levels. Moreover, SIRT3 activates enzymes responsible for the tricarboxylic acid (TCA) cycle and oxidative phosphorylation, thus enhancing mitochondrial respiration and ATP production, benefiting cardiovascular health. ABSTRACT: Hypertension can cause structural and functional abnormalities in the cardiovascular system, which can be attributed to both hemodynamic and nonhemodynamic factors. These alterations are linked with metabolic changes and are induced by pathological stressors. Sirtuins are enzymes that act as stress sensors and regulate metabolic adaptation by deacetylating proteins. Among them, mitochondrial SIRT3 performs a crucial role in maintaining metabolic homeostasis. Evidence from experimental and clinical studies has shown that hypertension-induced decreases in SIRT3 activity can lead to cellular metabolism reprogramming and, subsequently, increased susceptibility to endothelial dysfunction, myocardial hypertrophy, myocardial fibrosis, and heart failure. This review presents recent research advances in SIRT3-mediated metabolic adaptation in hypertensive cardiovascular remodeling.