A Role for Hydrogen Sulfide in Obesity‐dependent Microvascular Remodeling

Remodeling of the microvasculature occurs with obesity. Based on recent observations that impaired H 2 S signaling is associated with cardiovascular pathologies, the current study was designed to test the hypothesis that altered H 2 S homeostasis is involved in driving the remodeling process in a diet‐induced mouse model of obesity. The structural and passive mechanical properties of mesenteric arterioles isolated from 30 week‐old lean and obese mice were assessed using pressure myography. Vessels were loaded with the H 2 S indicator SF7‐AM and imaged confocally to determine H 2 S levels in the smooth muscle layer. Remodeling gene expression was assessed using qRT‐PCR and histological staining approaches used to quantify vessel collagen and elastin. Obesity was associated with increased arteriolar wall to lumen ratio, decreased compliance and a loss of elasticity. In addition, the vessel walls from obese animals contained more collagen and less elastin, as well increased expression of matrix metalloproteinases; connective tissue growth factor; collagen and fibronectin. Assessment of H 2 S levels revealed markedly lower levels in arterioles from obese compared to lean mice. Intriguingly, reversal of H 2 S depletion by overnight incubation with H 2 S donor reduced remodeling gene expression in arterioles from the obese mice. These data suggest that during obesity the microvasculature can undergo structural remodeling that is associated with depleted H 2 S, and demonstrate the potential for exogenous H 2 S repletion to modify the process. Supported by the American Heart Association and a Chicago Medical School/Advocate Lutheran General Hospital Pilot Grant.