Abstract 15733: Perivascular Adipose Tissue Triggers Vasa Vasorum Formation and Injury-Induced Neointimal Hyperplasia in Mice
Perivascular adipose tissue (PVAT) surrounds many conduit arteries and is a rich source of growth factors, cytokines and angiogenic molecules, but its role in vascular pathophysiology is unknown. We hypothesized that PVAT promotes vasa vasorum formational and exacerbates neointimal hyperplasia following vascular injury. PVAT (2–3 mg) was collected from the lesser curvature of the aortic arch of donor C57Bl/6J mice and transplanted to the carotid arteries of recipient high-fat diet (HFD)-fed LDLR−/− and chow-fed C57Bl/6 mice. Three weeks after PVAT transplantation, we executed wire injury of the carotid arteries in recipient mice. Two weeks after injury we quantified neointimal area. A subset of mice underwent PVAT transplantation in the absence of wire-injury to assess vasa vasorum (VV) formation. Carotid arteries were infused in situ with MICROFIL®, harvested and scanned with micro-computed tomography (CT) to visualize the VV. We found that transplanted perivascular adipose tissue caused a 4-fold increase in injury-induced neointimal area compared to sham-transplanted control LDLR−/− mice (29,000±12,000 μm2 n=7 vs. 7,000±7,000 μm2 n=5, respectively, p<0.02). The composition of the neointimal lesions was complex and rich in foam-like cells that expressed the macrophage marker F4/80. Transplanted PVAT, but not sham transplant, caused robust adventitial neovascularization between the injured vessel wall and the fat transplant. Two weeks after transplantation, PVAT induced the formation of VV interna (VVI) and venous VV (VVV) along the carotid arteries of chow-fed C57Bl/6J mice. Induction of VVI and VVV persisted for at least 7 months following PVAT transplantation in LDLR−/− mice. Our data demonstrate for the first time that PVAT locally modulates vascular biology by dramatically accelerating neointimal hyperplasia following vascular injury and inducing VV formation. These results have important implications for patients suffering from cardiovascular disease and metabolic disorders including diabetes and obesity.
- © 2010 by American Heart Association, Inc.