Native Low-Density Lipoprotein Increases Endothelial Cell Nitric Oxide Synthase Generation of Superoxide Anion

• DOI: 10.1161/01.res.77.3.510
• Publication Date: 2012-06-12T00:47:05Z
• Authors: Kirkwood A. Pritc...; Laura Groszek; David M. Smalley; William C. Sessa; Mingdan Wu; Patricio Villalon; Michael S. Wolin; Michael B. Stemerman
• Keywords: Nitrotyrosine; Low-density lipoprotein

Abstract To examine mechanisms by which native low-density lipoprotein (n-LDL) perturbs endothelial cell (EC) release of superoxide anion (O 2 − ) and nitric oxide (NO), ECs were incubated with n-LDL at 240 mg cholesterol per deciliter for 4 days media changes every 24 hours. increases EC O more than fourfold nitrite production 57%. In the conditioned from day-4 incubations, total nitrogen oxides 20 times control (C-EC) levels. However, did not alter NO synthase (eNOS) enzyme activity as measured [ 3 H]citrulline assay. N ω -Nitro- l -arginine methyl ester, a specific inhibitor eNOS activity, C-EC >300% but decreases LDL-treated (LDL-EC) >95%. -Arginine inhibits LDL-ECs >95% effect . Indomethacin SKF 525A partially attenuate LDL-induced in ≈50% 30%, respectively. Thus, production, likelihood formation peroxynitrite (ONOO ), potent oxidant. levels nitrotyrosine, stable oxidation product ONOO , tyrosine ≈50%. spite this increase oxidative metabolism, analysis thiobarbituric acid substances reveals that no significant occur during 24-hour incubations ECs. These data indicate directly metabolism uncouples to generation Such may represent one earliest perturbations atherogenesis.