The role of nitric oxide on rosuvastatin-mediated S-nitrosylation and translational proteomes in human umbilical vein endothelial cells

Background: the pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors (statins),which are independent from their cholesterol-lowering action,have been widely recognized in various biological systems. statins can affect endothelial homeostasis,which is partly modulated by the production of nitric oxide (no). however,it is unclear how statin/no-mediated posttranslational s-nitrosylation of endothelial proteins and changes in translational profiles may benefit endothelial integrity. therefore,it is important to understand the statin/no-mediated s-nitrosylation in endothelial cells.results: rosuvastatin treatment of human umbilical vein endothelial cells (ecs) enhanced the enzymatic activity of endothelial nitric oxide synthase (enos) and the expression of 78 s-nitrosoproteins. among these s-nitrosoproteins,we identified 17 proteins,including protein disulfide bond isomerase,phospholipase c,transaldolase and heat shock proteins. furthermore,a hydrophobic cys66 was determined as the s-nitrosylation site of the mitochondrial hsp70. in addition to the statin-modulated posttranslational s-nitrosylation,changes in the no-mediated translational proteome were also observed. seventeen major proteins were significantly upregulated after rosuvastatin treatment. however,12 of these proteins were downregulated after pretreating ecs with an enos inhibitor (l-name),which indicated that their expression was modulated by no.conclusions: ecs treated with rosuvastatin increase enos activation. the increased no production is involved in modulating s-nitrosylation and translation of proteins. we provide further evidence of the pleiotropic effect of rosuvastatin on endothelial physiology. © 2012 huang et al.; licensee biomed central ltd.