Oxidized Low-Density Lipoprotein Activates p66 Shc via Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1, Protein Kinase C-β, and c-Jun N-Terminal Kinase Kinase in Human Endothelial Cells

• DOI: 10.1161/atvbaha.111.229260
• Publication Date: 2011-08-05T04:23:23Z
• Authors: Yi Shi; Francesco Cosentino; Giovanni G. Camici; Alexander Akhmedov; Paul M. Vanhoutte; Felix C. Tanner; Thomas F. Lüscher
• Keywords: c-jun

Deletion of the mitochondrial gene p66(Shc) protects from endothelial dysfunction and atherosclerotic plaque formation in mice fed a high-fat diet. However, molecular mechanisms underlying this beneficial effect have not yet been delineated. The present study was designed to elucidate proatherogenic by which mediates oxidized low-density lipoprotein (oxLDL) uptake endothelium, critical step formation.Incubation human aortic cells with oxLDL led phosphorylation at Ser36. Inhibition lectin-like receptor-1 prevented phosphorylation, confirming that is mediated receptor-1. OxLDL also increased protein kinase C β(2) (PKCβ(2)) both Thr641 Ser660, as well c-Jun N-terminal (JNK). Furthermore, inhibition PKCβ(2) activation JNK, suggesting PKCβ2 upstream JNK. Finally, silencing blunted oxLDL-induced O(2)(-·) production, underscoring role oxidative stress cells.In we provide mediating previously observed atherogenic properties p66(Shc). Taken together, our data set stage for design novel therapeutic tools retard atherogenesis through