Abstract 19048: Tissue-Specific Regulation of Phospholipase C Beta-3 by Asymmetric Dimethylarginine (ADMA)

Elevated concentrations of the endogenous NO synthase inhibitor ADMA correlate with endothelial dysfunction and increased cardiovascular risk. ADMA is degraded by the enzyme DDAH. DDAH1-transgenic (DDAH1) mice show an increased NO production and are protected against inflammatory responses in graft coronary artery disease and ischemia reperfusion injury. The aim of this study was to identify ADMA-regulated genes in aortic tissue. Microarray gene expression analyses were performed in aortic tissue of DDAH1 male mice, wild-type littermates (WT), and C57Bl/6 (C57) mice with or without chronic ADMA infusion (50 mg/kg/body weight) via osmotic minipumps. DDAH1 mice showed lower ADMA plasma concentrations (DDAH1 vs. WT; 0.52±0.04 vs. 0.68±0.05 μmol/l, p<0.05) determined by LC-MS/MS, whereas ADMA-treated animals presented high ADMA levels (C57 vs. C57+ADMA; 0.83±0.03 vs. 3.30±0.21 μmol/l, p<0.001). Chronic ADMA infusion and DDAH1 overexpression resulted in a significant up- and downregulation of genes, particular...