Abstract 35: Atheroprotective Effects of Adiponectin Overexpression in a Model of AngII-Accelerated Atherosclerosis
Adiponectin, an adipocytokine derived from adipose tissue, exerts anti-inflammatory and anti-atherogenic effects on vascular cells. Although low plasma adiponectin levels are associated with the metabolic syndrome, diabetes and cardiovascular disease, it is unknown whether elevation of adiponectin levels protects against angiotensin II (AngII)-mediated vascular inflammation and accelerated atherosclerosis. Here, we tested the hypothesis that increasing plasma adiponectin levels provides therapeutic benefit by inhibiting vascular actions of AngII promoting vascular inflammation and accelerated atherosclerosis. Low-density lipoprotein receptor-deficient (LDLR-/-) mice fed high-fat and infused with Ang-II were injected adenovirus expressing GFP (Ad-GFP) or mouse adiponectin (Ad-APN). After 8 weeks, plasma adiponectin levels were 5-fold higher in Ad-APN than Ad-GFP. This was accompanied by significant elevation of plasma HDL in Ad-APN mice (24% elevation vs ad-GFP). Quantification of atherosclerosis revealed a significant inhibition of atherosclerosis in Ad-APN (45% reduction vs Ad-GFP). Gene expression analyses revealed that adiponectin substantially inhibited mRNA levels of inflammatory and atherogenic genes (CD68, ICAM-1, AT-1R, osteopontin, MCP-1 and CCR2, scavenger receptors, SRA-1 and CD36) in the aortic wall. Interestingly, adiponectin increased expression of anti-inflammatory cytokine, 1L-10 and the reverse cholesterol transport genes, ABCA1 and ABCG1 in the aortic wall. Furthermore, adiponectin increased hepatic ABCA1 and PPAR-alpha expression. These data strongly support the concept that increasing plasma adiponectin levels is an effective therapeutic strategy to inhibit AngII-mediated vascular inflammation and accelerated atherosclerosis.
- © 2012 by American Heart Association, Inc.