title: HIV-1-induced amyloid beta accumulation in brain endothelial cells is attenuated by simvastatin.
abstract: HIV-1-infected brains are characterized by increased amyloid deposition. To study the influence of HIV-1 on amyloid beta (Abeta) homeostasis at the blood-brain barrier (BBB) level, we employed a model of brain microvascular endothelial cells exposed to HIV-1 in the presence or absence of Abeta. HIV-1 markedly increased endogenous Abeta levels and elevated accumulation of exogenous Abeta. Simvastatin, the HMG-CoA reductase inhibitor, blocked these effects. We next evaluated the effects of HIV-1 and/or simvastatin on expression of the receptor for lipoprotein related protein (LRP1) and the receptor for advanced glycation end products (RAGE), known to regulate Abeta transport across the BBB. LRP1 expression was not affected by HIV-1; however, it was increased by simvastatin. Importantly, simvastatin attenuated HIV-1-induced RAGE expression. These results suggest that HIV-1 may directly contribute to Abeta accumulation at the BBB level. In addition, statins may protect against increased Abeta levels associated with HIV-1 infection in the brain.
authors: Department of Neurosurgery, University of Kentucky Medical Center, Lexington, KY 40536, USA.
authors: Ibolya E
authors: IE
authors: András
authors: Sung Yong
authors: SY
authors: Eum
authors: Wen
authors: W
authors: Huang
authors: Yu
authors: Y
authors: Zhong
authors: Bernhard
authors: B
authors: Hennig
authors: Michal
authors: M
authors: Toborek
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D001921:Brain / Q000166:cytology; D002461:Cell Line, Transformed; D018920:Coculture Techniques / Q000379:methods; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D005786:Gene Expression Regulation / Q000187:drug effects; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010446:Peptide Fragments; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C078592:amyloid beta-protein (1-40); D019821:Simvastatin