Abstract 14910: Vascular Cells Originating From Perivascular Adipose Tissue Contribute to Vasa Vasorum Neovascularization in Atherosclerosis

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Introduction: Proliferation of vasa vasorum (VV) is observed in the adventitia of arteries with atherosclerotic plaques. It was reported that fat tissue transplantation to carotid artery exaggerated neointimal formation and VV proliferation after wire injury in a hypercholesterolemic mouse model. However, there is no in vivo histological evidence that vascular cells originating from perivascular adipose tissue (PAT) contribute to VV neovascularization. Methods: We established a new mouse model of atherosclerosis, in which the carotid artery is partially ligated (CPL) and exogenous adipose tissue is transplanted in the perivascular area (PVAT). The three branches (external and internal carotid, occipital) of the left carotid artery (LCA) of 20- to 25- week-old male apolipoprotein E-deficient (ApoE-/-) mice were ligated. Then epididymal adipose tissue from a donor ApoE-/- mouse was transplanted around the LCA (CPL+PVAT, n=5). Carotid partial ligation alone was performed as a control (CPL, n=3). After 8 weeks, on western type diet, LCA was harvested with PAT after biotinylated-Lycopersicon Esculentum (Tomato) lectin perfusion staining. Next, epididymal fat tissue from a male enhanced green fluorescent protein (EGFP) mouse was transplanted around the LCA of another set of male ApoE -/- mice after CPL (n=4). After 8 weeks, LCA was harvested with PAT after perfusion staining of microvessels, embedded in plastic resin, and observed under a confocal microscope. Results: The transplanted adipose tissue engrafted and atherosclerotic lesion developed in LCAs. Intima/media ratio of CPL+PVAT group was similar with that of CPL alone group (p=0.39). Whereas, VV density in adventitial area (outside the elastic lamina within a distance of the thickness of neointima plus media, excluding PAT) near three -fold increased than CPL alone group (p<0.05). In the EGFP fat transplanted mice, a significant portion of VV was GFP positive (GFP positive /total microvessels in adventitia: 12.5 ± 6.2 % ). Conclusions: The vascular cells derived from PAT contribute to VV neovascularization, at least in part, in atherosclerosis.