Joseph Candela1, Rui Wang1, Carl White2. 1. From the Department of Physiology and Biophysics, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL (J.C., C.W.); and Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Canada (R.W.). 2. From the Department of Physiology and Biophysics, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL (J.C., C.W.); and Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Canada (R.W.). carl.white@rosalindfranklin.edu.
Abstract
OBJECTIVE: The function of perivascular adipose tissue as an anticontractile mediator in the microvasculature is lost during obesity. Obesity results in inflammation and recruitment of proinflammatory macrophages to the perivascular adipose tissue that is paralleled by depletion of the vasorelaxant signaling molecule hydrogen sulfide (H2S) in the vessel. The current objective was to assess the role of macrophages in determining vascular [H2S] and defining how this impinged on vasodilation. APPROACH AND RESULTS: Contractility and [H2S] were measured in mesenteric resistance arterioles from lean and obese mice by using pressure myography and confocal microscopy, respectively. Vasodilation was impaired and smooth muscle and endothelial [H2S] decreased in vessels from obese mice compared with those from lean controls. Coculturing vessels from lean mice with macrophages from obese mice, or macrophage-conditioned media, recapitulated obese phenotypes in vessels. These effects were mediated by low molecular weight species and dependent on macrophage inducible nitric oxide synthase activity. CONCLUSIONS: The inducible nitric oxide synthase activity of perivascular adipose tissue-resident proinflammatory macrophages promotes microvascular endothelial dysfunction by reducing the bioavailability of H2S in the vessel. These findings support a model in which vascular H2S depletion underpins the loss of perivascular adipose tissue anticontractile function in obesity.
OBJECTIVE: The function of perivascular adipose tissue as an anticontractile mediator in the microvasculature is lost during obesity. Obesity results in inflammation and recruitment of proinflammatory macrophages to the perivascular adipose tissue that is paralleled by depletion of the vasorelaxant signaling molecule hydrogen sulfide (H2S) in the vessel. The current objective was to assess the role of macrophages in determining vascular [H2S] and defining how this impinged on vasodilation. APPROACH AND RESULTS: Contractility and [H2S] were measured in mesenteric resistance arterioles from lean and obesemice by using pressure myography and confocal microscopy, respectively. Vasodilation was impaired and smooth muscle and endothelial [H2S] decreased in vessels from obesemice compared with those from lean controls. Coculturing vessels from lean mice with macrophages from obesemice, or macrophage-conditioned media, recapitulated obese phenotypes in vessels. These effects were mediated by low molecular weight species and dependent on macrophage inducible nitric oxide synthase activity. CONCLUSIONS: The inducible nitric oxide synthase activity of perivascular adipose tissue-resident proinflammatory macrophages promotes microvascular endothelial dysfunction by reducing the bioavailability of H2S in the vessel. These findings support a model in which vascular H2S depletion underpins the loss of perivascular adipose tissue anticontractile function in obesity.
Authors: Matteo Ottolini; Kwangseok Hong; Eric L Cope; Zdravka Daneva; Leon J DeLalio; Jennifer D Sokolowski; Corina Marziano; Nhiem Y Nguyen; Joachim Altschmied; Judith Haendeler; Scott R Johnstone; Mohammad Y Kalani; Min S Park; Rakesh P Patel; Wolfgang Liedtke; Brant E Isakson; Swapnil K Sonkusare Journal: Circulation Date: 2020-02-03 Impact factor: 29.690
Authors: Hong S Lu; Ann Marie Schmidt; Robert A Hegele; Nigel Mackman; Daniel J Rader; Christian Weber; Alan Daugherty Journal: Arterioscler Thromb Vasc Biol Date: 2018-10 Impact factor: 8.311