Periadventitial Adipose Tissue Promotes Endothelial Dysfunction via Oxidative Stress in Diet-Induced Obese C57Bl/6 Mice

Abstract

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 C57Bl/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 C57Bl/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

Long Term High-Fat Diet-Induced Modification of Vascular Wall and Perivascular Adipose Tissue-Mediated Oxidative Stress: Consequences for Endothelium-Independent Vascular Function in Rats

“…The negative effect of SOD on PE-induced contraction found in HFD rings confirms that O2·-mediated this procontractile potency. These results give further information concerning the triggers of HFD effect, when compared with previous data from Bourgoin, et al [14] and Ketonen, et al [16] who have reported that HFD induced an increase in aortic wall gp91phox (NOX2) protein and mRNA levels. In addition, the enhanced procontractile potency of the aortic wall of HFD rats could be subsequent to increased H 2 O 2 generation.…”

“…Indeed, PVAT from obese subjects with metabolic syndrome is devoid of any anticontractile property [6]. Although diet-induced decrease of endothelium-dependent vasorelaxation is well documented [12,[14][15][16], a direct effect of diet alterations, especially increased fat intake, on vascular smooth muscle cells has received much less attention.…”

Obesity, But Not High Fat Diet, Impairs Lymphatic Function

“…37,38 This is important because perivascular inflammation has a key role in the pathological outcomes of obesity on the blood vascular system by diverse mechanisms including altered expression of adipokines, impaired nitric oxide signaling and increased production of reactive oxygen species. 7,39,40 These effects are compounded by infiltration of macrophages that phagocytose necrotic adipocytes, leading to the release of long-chain FFA 41 that, in turn, have deleterious effects on endothelial cells. 6,31,42 Indeed, in our studies we observed the presence of numerous CLS, and close association of large lipid droplets with lymphatic vessels, in the subcutaneous tissues of obese mice.…”

Pericoronary Adipose Tissue as Possible Supply Site and Storage for Lipoproteins in Human Coronary Artery

“…Perivascular adipocytes (PVA) deliver substantial quantities of metabolically dynamic substances with both endocrine and paracrine actions [19]; PVA of human internal thoracic artery release NO [20]; PVA discharges nicotinamide adenine dinucleotide phosphateoxidase in mice [21]; rat PVA discharge compliment [23,22]; rat PVA discharge metylpalmitate ester [23]; different substances, for example, plasminogen activator inhibitor-1 and interleukin-6 are contained in epicardial adipose tissue in patients with acute coronary syndrome [24]; cultured human epicardial adipose tissues release glutation S-transferase P and ApoA1 [25]. But, reports depicting release and storage of lipoproteins from human PVA, including PCAT, to the nearby vessel wall were not found.…”