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Perivascular adipose tissue ( PVAT ) is implicated in the development of vascular diseases; however, the roles of  PVAT  on  OPN  expression in diabetic vasculature remain to be determined. This study investigated the role of adipokines derived from diabetic  PVAT  in regulating the vascular expression of  OPN  and explored the mechanisms involved. Aortic sections of ob/ob and high‐fat diet ( HFD )‐induced obese ( DIO ) mice showed an increased expression of  OPN , which was paralleled by increased amounts of  PVAT  characterized by enlargement of adipocytes. In the earlier phase of  HFD  feeding, macrophage infiltration was mainly localized to the area of  PVAT  at which adipocytes were enlarged, suggesting a potential link of activated adipocytes to macrophage infiltration.  PVAT  sections of ob/ob and  DIO  mice revealed a significantly greater number of macrophages with increased expression of adipokines, including resistin and visfatin. The distribution of resistin in  PVAT  mostly co‐localized with macrophages, while visfatin was expressed in macrophages and other cells. In  in vitro  studies,  OPN  expression in vascular smooth muscle cells ( VSMCs ) co‐cultured with  PVAT  of  DIO  mice was significantly increased, which was attenuated by a resistin‐neutralizing antibody. Likewise, resistin up‐regulated expression of   OPN    mRNA  and protein in cultured  VSMCs  and the pivotal role of  AP ‐1 in resistin‐induced  OPN  transcription was demonstrated. Resistin produced by  PVAT  plays a pivotal role in the up‐regulated expression of  OPN  in the diabetic vasculature via a signalling pathway that involves activation of  AP ‐1. © 2013 The Authors.  Journal of Pathology  published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britainand Ireland.

Resistin derived from diabetic perivascular adipose tissue up‐regulates vascular expression of osteopontin via the AP ‐1 signalling pathway