Conclusions
Perivascular visceral fat leads to endothelial dysfunction and accelerated atherosclerosis. This proatherogenic effect of perivascular adipose tissue is blocked by neutralization of Psgl-1.
Objective
Epicardial adipose tissue is associated with coronary artery disease, however the causal relationship between perivascular adipose tissue and local atherogenesis is unclear.
Results
Apolipoprotein E deficient (ApoE(-/-)) mice underwent transplantation of visceral or subcutaneous adipose tissue immediately adjacent to the right common carotid artery. Carotid arteries with fat transplants were analyzed for atherosclerosis by surface oil-red-O staining and cross-sectional analysis. Vascular function of the carotid arteries was assessed using pressure myography. Visceral fat transplants were also performed to ApoE(-/-) mice with neutralization of P-selectin glycoprotein ligand-1 (Psgl-1). Atherosclerosis surface area and lesion thickness were greater in mice receiving the perivascular visceral fat compared to the subcutaneous fat. Mice with visceral fat transplants also displayed more complicated atherosclerotic lesions with evidence of atherothrombosis. Serum Mcp-1 was higher in mice receiving visceral fat transplants compared to subcutaneous transplants. Visceral fat transplantation also caused impaired endothelial-dependent relaxation of the carotid artery. Psgl-1 deficiency or neutralization of Psgl-1 with an anti-Psgl-1 antibody was protective against perivascular visceral adipose tissue-induced atherosclerosis and was associated with reduced Mcp-1 levels. Conclusions: Perivascular visceral fat leads to endothelial dysfunction and accelerated atherosclerosis. This proatherogenic effect of perivascular adipose tissue is blocked by neutralization of Psgl-1.