Circ Res 2014 Aug 5;115(4):450-9. Epub 2014 Jun 5.
From the Department of Anesthesiology and Critical Care Medicine (D.P., A.B., Y.J.O., F.C., Y.B., J.H.K., J.S., D.E.B., L.H.R.), Biomedical Engineering (J.S., D.E.B., L.H.R.), and Cell Biology, Pediatrics, Center for Cell Dynamics (L.H.R.), Mass Spectrometry and Proteomics Facility (T.N.B., R.N.C.), and Departments of Medicine and Biological Chemistry (J.V.E.), Johns Hopkins University School of Medicine, Baltimore, MD; and Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (A.T.R.).
Rationale: Increased arginase activity contributes to endothelial dysfunction by competition for l-arginine substrate and reciprocal regulation of nitric oxide synthase (NOS). The rapid increase in arginase activity in human aortic endothelial cells exposed to oxidized low-density lipoprotein (OxLDL) is consistent with post-translational modification or subcellular trafficking.
Objective: To test the hypotheses that OxLDL triggers reverse translocation of mitochondrial arginase 2 (Arg2) to cytosol and Arg2 activation, and that this process is dependent on mitochondrial processing peptidase, lectin-like OxLDL receptor-1 receptor, and rho kinase. Read More