HIV-1-induced amyloid beta accumulation in brain endothelial cells is attenuated by simvastatin |
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| Authors: | Ibolya E. András Sung Yong Eum Wen Huang Yu Zhong Bernhard Hennig Michal Toborek |
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| Affiliation: | 1. Department of Chemistry, University of Missouri-Kansas City, Kansas City, Missouri 64110;2. Laboratory of Future Nanomedicines and Theoretical Chronopharmaceutics, Division of Pharmaceutical Science, University of Missouri-Kansas City, Kansas City, Missouri 64108;1. Institute of Pathophysiology and Immunology, Medical University of Graz, Graz, Austria;2. Molecular Neurodegeneration, Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany;3. Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institute Huddinge, Huddinge, Sweden;4. Laboratory of Neurochemistry and Molecular Neurobiology, Division of Molecular Biology, Rudjer Boskovic Institute, Zagreb, Croatia;5. School of Biological Sciences, Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia |
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| Abstract: | HIV-1-infected brains are characterized by increased amyloid deposition. To study the influence of HIV-1 on amyloid beta (Aβ) 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 Aβ. HIV-1 markedly increased endogenous Aβ levels and elevated accumulation of exogenous Aβ. 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 Aβ 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 Aβ accumulation at the BBB level. In addition, statins may protect against increased Aβ levels associated with HIV-1 infection in the brain. |
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