Abstract 525: Transplanted LRP1-Deficient Periaortic Adipose Tissue Accelerates Atherosclerosis in Carotid Arteries of LDL Receptor Knockout Mice
Perivascular adipose tissue (PVAT) expands in obesity and is anatomically colocalized with atherosclerotic plaques in humans. Moreover, PVAT inflammation is upregulated in the setting of atherosclerosis. Local factors expressed in PVAT that influence adipose tissue inflammation and adipocyte expansion could modulate “outside-in” signals involved in the progression of atherosclerosis. Previous studies have shown that mice with adipose tissue deficient for the LDL receptor-related protein 1 (ad-Lrp1-/-) display reduced adipocyte size and resistance to diet-induced obesity. To assess the contribution LRP1 in PVAT on the progression of atherosclerosis, we utilized an adipose allograft model. Briefly, PVAT taken from the aortic arch of ad-Lrp1-/- and ad-Lrp1+/+mice were transplanted to the left common carotid arteries of LDL-receptor deficient (Ldlr-/-) mice. Following a four week engraftment period mice were fed western diet for 12 weeks. Carotid arteries were then analyzed for lesion formation and the surrounding adipose tissue was analyzed for inflammatory markers. Carotid arteries of LDLR-/- mice receiving ad-LRP1-/- transplanted adipose tissue exhibited >3 fold increase in plaque size compared to mice transplanted with ad-Lrp1+/+ adipose tissues. Plasma lipid levels and atherosclerotic lesions in the contralateral carotid arteries, without PVAT transplant, were similar between the two recipient groups. When compared to wild-type, ad-Lrp1-/- transplanted PVAT had a 1.9 fold increased number of CD68+ cells determined by both immunohistochemistry and mRNA. Pro-inflammatory cytokines, IL6 (2.7 fold), TNFα (4.7 fold), and MCP1 (2.1 fold) mRNA were also increased in ad-Lrp1-/-transplanted PVAT. In addition, ad-Lrp1-/- transplanted PVAT retained a decreased cell size as observed prior to and after transplantation indicating either increased triglyceride lipolysis or defective triglyceride storage. These findings suggest that deficiency of LRP1 in PVAT accelerates atherosclerosis via enhancing local vascular inflammation.
Author Disclosures: D.G. Kuhel: None.
- © 2015 by American Heart Association, Inc.