Abstract 12285: Transplantation of High-Cholesterol Diet-Induced Inflammatory Periaortic Adipose Tissue Exaggerates Atherosclerosis Development in Recipient ApoE Deficient Mice
BACKGROUND: Perivascular adipose tissue has been reported to contribute to vascular function and remodeling through various kinds of adipose-derived factors; however, the causal relation between perivascular adipose tissue and atherosclerosis remains undefined.
METHOD AND RESULT: We first examined the phenotypic changes of periaortic adipose tissue (PAT) surrounding the thoracic aorta in apoE deficient (apoE-/-) mice after 4 weeks of high-cholesterol diet. The expression levels of adipocyte differentiation-related genes (SREBP1c, PPARγ, FABP4), inflammatory cytokines (TNFα, IL-6, MCP-1), and macrophage marker (CD68, CD11c) were dramatically increased compared with those in apoE-/- mice fed a chow diet (P≤0.05). These findings were not observed in epididymal white adipose tissue, suggesting that depot-specific inflammatory response was elicited by feeding a high-cholesterol diet. Moreover, this inflammatory response was completely inhibited by treatment with Olmesartan (1mg/kg/day). To examine whether PAT-specific inflammatory response promotes atherosclerosis development, we developed PAT transplantation model, in which isolated PAT from 16-weeks-old donor apoE-/- mice fed a 8 weeks of high-cholesterol diet (PAT-HCD) or chow diet (PAT-CD) was transplanted into 20-weeks-old recipient apoE-/- mice alongside the abdominal aorta. Oil-red-O staining 4 weeks later showed a 2.1 fold-increase in atherosclerotic lesion area of distal abdominal aorta in PAT-HCD mice compared with those in sham control mice (P≤0.05), whereas no significant increase was observed in PAT-CD mice, suggesting that PAT-specific inflammatory response primarily contributes to the progression of atherosclerosis in a paracrine manner. In contrast, atherosclerosis development in the recipient mice whose transplanted PAT was isolated from ARB treated donor mice was completely diminished to the similar level as sham control mice.
CONCLUSION: Our findings demonstrated for the first time that high-cholesterol diet-induced PAT-specific inflammatory response promotes the development of atherosclerosis, and phenotypic modulation of PAT could be potential therapeutic strategy for preventing atherosclerotic disease.
- © 2013 by American Heart Association, Inc.