title: Endogenous hydrogen sulfide in perivascular adipose tissue: role in the regulation of vascular tone in physiology and pathology.
abstract: 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.
authors.affiliation: Department of Pathophysiology, Medical University, ulica Jaczewskiego 8, 20-090 Lublin, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Bełtowski
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology; D002320:Cardiovascular Physiological Phenomena; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D009129:Muscle Tonus / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology; D014652:Vascular Diseases / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D002186:Cannabinoids; D006862:Hydrogen Sulfide