期刊
CIRCULATION JOURNAL
卷 74, 期 7, 页码 1479-1487出版社
JAPANESE CIRCULATION SOC
DOI: 10.1253/circj.CJ-09-0661
关键词
Endothelial dysfunction; Obesity; Perivascular fat; Vasoconstriction
资金
- Academy of Finland
- Sigrid Juselius Foundation
- Aili and Aarne Turunen Foundation
- Finnish Cultural Foundation
Background: Biological substances derived from perivascular fat modulate vascular tone, thus alterations in periadventitial adipose tissue (PVAT) may aggravate endothelial dysfunction in obesity. Methods and Results: Male C57BI/6 mice were fed either a high-fat diet or standard laboratory chow for 8 months. Vascular responses were studied in organ bath chambers from abdominal aortic ring preparations in the absence or presence of PVAT. The amount of PVAT as well as the cross-sectional area of adipocytes were increased in obese mice. In the presence of PVAT, obese aortas displayed impaired endothelium-dependent vasodilation whereas endothelium-independent vasodilatation was unaltered. Endothelium-dependent vasodilatation was restored after removal of PVAT and after reducing superoxide and hydrogen peroxide formation in the vascular wall by Tiron or polyethylene-glycol-catalase, respectively. PVAT from obese mice showed increased formation of hydrogen peroxide and superoxide. The PVAT-derived oxidative stress was abolished by pretreatment with the reduced nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase inhibitor, apocynin. The anti-contractile function of PVAT found in lean mice was completely abolished in obese mice, but partially restored after pretreatment with Tiron. The mRNA expressions of monocyte chemotactic protein-1, leptin and NADPH oxidase were markedly higher in the PVAT of obese than lean mice. Conclusions: PVAT promotes endothelial dysfunction in diet-induced obese C57BI/6 mice via mechanisms that are linked to increased NADPH oxidase-derived oxidative stress and increased production of pro-inflammatory cytokines. (Circ J 2010; 74: 1479 1487)
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