# Urolithin A alleviates vascular remodeling through mitochondrial SIRT3-mediated SOD2 deacetylation and antioxidation in hypertensive rats

## TL;DR

Urolithin A reduces high blood pressure and vascular changes in rats by boosting mitochondrial activity and reducing oxidative stress.

## Contribution

This study reveals that Urolithin A alleviates hypertension through SIRT3-mediated SOD2 deacetylation and mitochondrial antioxidation.

## Key findings

- Urolithin A reduces vascular smooth muscle cell proliferation and migration in hypertensive rats.
- Urolithin A increases SOD2 activity and decreases mitochondrial ROS levels via SIRT3.
- Long-term Urolithin A treatment attenuates vascular remodeling and hypertension in SHR rats.

## Abstract

Urolithin A (UA) is a natural polyphenolic compound produced by gut bacteria. Vascular remodeling contributes to hypertension, and vascular smooth muscle cells (VSMCs) proliferation and migration are important processes in vascular remodeling.

VSMCs were obtained from the thoracic aorta of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Intraperitoneal injections of UA (50 mg/kg, every 2 days for 4 weeks) were performed in SHR.

UA attenuated proliferation and migration, reduced mitochondrial reactive oxygen species (mitoROS) levels, and increased SOD2 activity in VSMCs of SHR, which were prevented by SOD2 knockdown. UA promoted mitochondrial short-length SIRT3 (SL-SIRT3) production and SOD2 deacetylation. SIRT3 inhibitor 3-TYP abolished the effects of UA on SOD2 deacetylation, mitoROS levels and VSMCs proliferation and migration. Repeated intraperitoneal injection of UA every 2 days for 4 weeks attenuated vascular remodeling and hypertension, increased SL-SIRT3 levels and SOD2 activity, and reduced SOD2 acetylation and mitoROS levels in aorta and mesenteric arteries of SHR.

UA attenuates VSMCs proliferation and migration in SHR by increasing mitochondrial SL-SIRT3 level, and subsequent SOD2 deacetylation and mitoROS reduction in SHR. Long-term administration of UA attenuates vascular remodeling, hypertension and oxidative stress in SHR.