Abstract 5259: Endovascular Injury Alters Adipocytokine Profile of the Periadventitial Adipose Tissue
Recent evidence suggests that adipose tissue is an endocrinal organ that secretes not only proinflammatory cytokines but also anti-inflammatory adipocytokines such as adiponectin. Obesity is an important risk factor for restenosis after angioplasty. Here we investigated the role of periadventitial adipose tissues (PAT) in vascular remodeling after endovascular injury. First, endovascular injury significantly down-regulated adiponectin and up-regulated proinflammatory adipocytokines, TNF-alpha, IL-6, PAI-1 and MCP-1 within PAT in models of murine femoral artery wire injury, rat iliac artery balloon injury and rat aorta ex vivo balloon injury. Second, diet-induced obesity augmented endovascular injury-induced up-regulation of proinflammatory adipocytokines within PAT (p<0.05) and neointimal hyperplasia (p<0.05) compared with standard chow diet in wild-type mice. Third, up-regulation of proinflammatory adipocytokines within PAT by endovascular injury was significantly blunted in TNF-alpha deficient mice (p<0.05). Neointima formation was attenuated in TNF-alpha deficient mice compared with compared with wild-type mice (p<0.05). Furthermore, perivascular delivery of TNF-alpha to the femoral artery using osmotic minipump enhanced endovascular injury-induced up-regulation of proinflammatory adipocytokines within PAT (p<0.05) and neointimal hyperplasia (p<0.05) compared with contralateral PBS delivered artery in TNF-alpha deficient mice. Fourth, the stimulation of TNF-alpha caused significant down-regulation of adiponectin expression and up-regulation of IL-6, PAI-1 and MCP-1 in 3T3L1-derived adipocytes (p<0.01). However, in vitro stretch did not change adipocytokine profiles in the differentiated 3T3-L1 cells. Endovascular injury alters the profiles of perivascular adipocytokines expression. Obesity augments these adipocytokines changes that may contribute to vascular remodeling. Peri-vascular adipose tissues may influence vascular remodeling following angioplasty via TNF-alpha-mediated signaling.