HIV-1-induced amyloid beta accumulation in brain endothelial cells is attenuated by simvastatin.
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.
András
Ibolya E
IE
Department of Neurosurgery, University of Kentucky Medical Center, Lexington, KY 40536, USA.
Eum
Sung Yong
SY
Huang
Wen
W
Zhong
Yu
Y
Hennig
Bernhard
B
Toborek
Michal
M
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
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