Hydrogen sulfide (H₂S) is synthesized from l-cysteine by cystathionine β-synthase (CBS) or cystathionine γ-lyase (CSE), and is enzymatically metabolized in mitochondria by sulfide:quinone oxidoreductase (SQR). Recent studies have indicated that H₂S is synthesized by CSE in perivascular adipose tissue (PVAT), and is responsible for the anticontractile effect of PVAT on adjacent vessels. The lipophilic statin atorvastatin increases PVAT-derived H₂S by suppressing its mitochondrial oxidation; the effect that results from statin-induced depletion of ubiquinone. Experimental obesity induced by a highly palatable diet has a time-dependent effect on H₂S in PVAT. Adipose tissue hypoxia suppresses H₂S oxidation and increases its level in short-term obesity not associated with insulin resistance. In contrast, in long-term obesity, insulin resistance and (or) hyperinsulinemia result in the down-regulation of CSE and H₂S deficiency, which is corrected by treatment with the insulin sensitizer rosiglitazone. In addition,cannabinoid CB₁ receptor agonist administered for 2 weeks increases H₂S by impairing mitochondria biogenesis. This indicates that the rate of mitochondrial H₂S oxidation plays an important role in the regulation of H₂S level in PVAT. Up-regulation of H₂S signaling in short-term obesity and (or) by elevated endocannabinoids may be a compensatory mechanism that maintains vascular tone, despite endothelial dysfunction.

PMID:

 

24117256

 

[PubMed – as supplied by publisher]