Τίτλος:
Aging modulates the influence of arginase on endothelial dysfunction in obesity
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objective-Arginase can reduce NO availability. In this study, we explored arginase as a determinant of endothelial dysfunction in small arteries from obese patients and its relationship with aging and microvascular remodeling. Approach and Results-Small arteries were dissected after subcutaneous fat biopsies and evaluated on a pressurized micromyograph. Endothelium-dependent vasodilation was assessed by acetylcholine, repeated under L-NAME (NG-nitro-L-arginine-methyl ester), N(ω)-hydroxy-nor-l-arginine (arginase inhibitor) and gp91ds-tat (NADPH [nicotinamide adenine dinucleotide phosphate oxidase] oxidase inhibitor) in vessels from young (age <30 years) control and obese and old (>30 years) control and obese subjects. Media-lumen ratio and amount of vascular wall fibrosis were used as markers of vascular remodeling. Amount of vascular superoxide anions and NO production were determined with immunofluorescence, whereas arginase expression was quantified using Western blot and quantitative polymerase chain reaction. Obese and older age groups had lower vascular NO, as well as higher media-lumen ratio, wall fibrosis, intravascular superoxide, and blunted inhibitory effect of L-NAME on acetylcholine versus controls and younger age groups. N(ω)-hydroxy-nor-l-arginine restored the acetylcholine-induced vasodilation in young and, to a lesser extent, in old obese subjects. This effect was abolished by addition of L-NAME. Gp91ds-tat increased the vasodilatory response to N(ω)-hydroxy-nor-l-arginine in old obese. Superoxide anions and arginase I/II levels were higher in the vascular wall of obese versus controls. Conclusions-Arginase contributes to microvascular endothelial dysfunction in obesity. Its impact is reduced by aging because of higher levels of vascular oxidative stress. Obesity is accompanied by accelerated microvascular remodeling, the extent of which is related to the amount of arginase in the vascular wall. © 2018 American Heart Association, Inc.
Συγγραφείς:
Masi, S.
Colucci, R.
Duranti, E.
Nannipieri, M.
Anselmino, M.
Ippolito, C.
Tirotta, E.
Georgiopoulos, G.
Garelli, F.
Nericcio, A.
Segnani, C.
Bernardini, N.
Blandizzi, C.
Taddei, S.
Virdis, A.
Περιοδικό:
Arteriosclerosis, Thrombosis, and Vascular Biology
Εκδότης:
Lippincott Williams and Wilkins
Λέξεις-κλειδιά:
acetylcholine; arginase; arginase 1; arginase ii; endothelial nitric oxide synthase; malonaldehyde; n(g) nitroarginine methyl ester; nicotinamide adenine dinucleotide phosphate; superoxide; unclassified drug; arginase; enzyme inhibitor; nitric oxide; reduced nicotinamide adenine dinucleotide phosphate oxidase; superoxide; vasodilator agent, adult; aging; Article; biopsy; body mass; case control study; clinical article; controlled study; endothelial dysfunction; enzyme activity; female; human; human tissue; immunofluorescence; immunofluorescence test; male; obesity; phenotype; polymerase chain reaction; priority journal; subcutaneous fat; vascular remodeling; Western blotting; age; aging; antagonists and inhibitors; artery; comparative study; drug effect; enzymology; metabolism; middle aged; obesity; oxidative stress; pathophysiology; signal transduction; vascularization; vasodilatation; young adult, Adult; Age Factors; Aging; Arginase; Arteries; Case-Control Studies; Enzyme Inhibitors; Female; Humans; Male; Middle Aged; NADPH Oxidases; Nitric Oxide; Obesity; Oxidative Stress; Signal Transduction; Subcutaneous Fat; Superoxides; Vascular Remodeling; Vasodilation; Vasodilator Agents; Young Adult
DOI:
10.1161/ATVBAHA.118.311074
