Advances in the Role of SIRT3 in Vascular Remodeling in Hypertension

Area of Science:

• Mitochondrial biology and cardiovascular pathophysiology.
• Molecular mechanisms of hypertension-induced vascular remodeling.

Background:

• Hypertension leads to detrimental vascular remodeling, including endothelial dysfunction, smooth muscle cell changes, fibrosis, and inflammation, contributing to cardiovascular morbidity.
• Sirtuin 3 (SIRT3), a mitochondrial deacetylase, is crucial for mitochondrial homeostasis, redox balance, and energy metabolism.

Purpose of the Study:

• To investigate the role of Sirtuin 3 (SIRT3) in hypertension-induced vascular remodeling.
• To elucidate the mechanisms by which SIRT3 deficiency exacerbates vascular injury in hypertension.

Main Methods:

• Analysis of SIRT3's impact on vascular smooth muscle cells, endothelial cells, macrophages, and perivascular adipose tissue.
• Investigation of SIRT3's regulation of mitochondrial reactive oxygen species, nitric oxide bioavailability, and inflammatory pathways like NLRP3 inflammasome.
• Assessment of SIRT3's role in fibroblast activation and transforming growth factor-β/Smad3 signaling.

Main Results:

• SIRT3 deficiency enhances mitochondrial reactive oxygen species production, promotes glycolysis, and drives vascular smooth muscle cell phenotypic switching and proliferation.
• SIRT3 protects endothelial cells from oxidative stress, preserves nitric oxide bioavailability, and mitigates vascular fibrosis by inhibiting fibroblast-to-myofibroblast transformation.
• SIRT3 attenuates vascular inflammation by regulating macrophage metabolism and inhibiting NLRP3 inflammasome activation; its deficiency worsens perivascular adipose tissue dysfunction.

Conclusions:

• SIRT3 acts as a critical mitochondrial regulator protecting against hypertension-induced oxidative stress and inflammation.
• Targeting SIRT3-dependent pathways presents a promising therapeutic strategy to restore vascular homeostasis and prevent hypertensive vascular remodeling.