Mechanisms of disease: paracine effects of adipose tissue, progenitor cell function, and epigenetics of diabetic vascular disease.

Abstract

![Graphic][1] Adipose tissue has been recognized as a source of cytokines that contributes to chronic inflammation in patients with metabolic syndrome and diabetes.1,2 Furthermore, perivascular epicardial adipose tissue has been related to cardiovascular risk factors and coronary artery calcification,3 as well as to the severity of coronary artery disease.4 Endothelial dysfunction is an early stage of atherosclerosis,5 and hence it is of interest to see how perivascular adipose tissue interferes with the control of vascular tone. The first paper in this issue, entitled ‘Tumour necrosis factor-alpha participates on the endothelin-1/nitric oxide imbalance in small arteries from obese patients: role of perivascular adipose tissue’ 6 by Agostino Virdis from the University of Pisa in Italy assessed the impact of the cytokine tumour necrosis factor-alpha (TNF-α) produced by vascular and perivascular tissue on the endothelin-1 (ET-1)7 and nitric oxide (NO) system,8 which are both altered in many disease states. To that end, small arteries from 16 obese subjects and 14 controls were mounted in a pressurized myograph, and endogenous ET-1 activity was assessed by adding the ETA blocker BQ-123. The contributions of TNF-α and NO were tested using the anti-TNF-α antibody infliximab and the inhibitor of the l-arginine pathway l-NAME ( N ω-nitro-l-arginine methylester). Obese subjects showed a blunted l-NAME-induced vasoconstriction (reflecting a reduced basal NO release), which was augmented by infliximab, while the relaxation to BQ-123 (reflecting basal ET-1 production) was attenuated by infliximab but unaffected by l-NAME. Interestingly, removal of perivascular adipose tissue reversed these effects. Obese subjects also produced more superoxide, which was decreased by the NADPH oxidase inhibitor apocynin, l-NAME, and BQ-123, and abolished by infliximab. An increased vascular expression of ET-1, ETA, and ETB receptors, and higher vascular and … [1]: /embed/inline-graphic-1.gif