Abstract 17989: Genetic Variability of Adiponectin Gene Defines the Biosynthesis Rate of Adiponectin in Adipose Tissue and Regulates Superoxide Generation in Human Arteries in vivo
Background: Adiponectin is an adipokine whose plasma levels are inversely associated with cardiovascular risk, although the underlying mechanisms are unknown. We examined the effect of genetic variability of adiponectin gene on the synthesis of adiponectin in pericardial adipose tissue, on circulating adiponectin levels and on global vascular function.
Methods: One hundred and sixty nine patients with coronary artery disease undergoing CABG were recruited. T45G and G276T polymorphisms on adiponectin gene were detected by PCR, while serum adiponectin was measured by ELISA. During CABG, IMA segments were obtained to determine total and NADPH-stimulated vascular O2- ex vivo, by using lucigenin-enhanced chemiluminescence. Pericardial adipose tissue (AT) obtained during CABG was cultured ex vivo for 4 hours and adiponectin's biosynthetic rate was quantified. Flow mediated dilatation and arterial distensibility were determined in the brachial artery by ultrasound.
Results: The genotype distribution for T45G was GG+GT: 21.7% and TT: 78.3%, while for G276T was GG: 50% and TG+TT: 50%. None of the 2 SNPs altered circulating adiponectin (A, ns: non significant) but 45TT and 276TT were associated with reduced adiponectin biosynthesis in AT (B; *p<0.05; **p<0.01). Furthermore genetic variability on adiponectin gene had a significant impact on FMD (C), brachial distensibility (D) and total (E) and NADPH-stimulated O2- (F) production from IMAs.
Conclusions: Even though T45G and G276T polymorphisms on adiponectin gene do not alter circulating adiponectin levels, they have a significant effect on adiponectin release from pericardial AT as well as on global vascular function in patients with coronary atherosclerosis. These findings provide new insights in the role of adiponectin in vascular biology.
- © 2010 by American Heart Association, Inc.