HIV-1-induced amyloid beta accumulation in brain endothelial cells is attenuated by simvastatin

Ibolya E. András; Sung Yong Eum; Wen Huang; Yu Zhong; Bernhard Hennig; Michal Toborek

doi:10.1016/j.mcn.2009.11.004

HIV-1-induced amyloid beta accumulation in brain endothelial cells is attenuated by simvastatin

Ibolya E. András, Sung Yong Eum, Wen Huang, Yu Zhong, Bernhard Hennig, Michal Toborek

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

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.

Original language	English
Pages (from-to)	232-243
Number of pages	12
Journal	Molecular and Cellular Neuroscience
Volume	43
Issue number	2
DOIs	https://doi.org/10.1016/j.mcn.2009.11.004
State	Published - Feb 2010

Bibliographical note

Funding Information:
pYK-JRCSF was obtained from the AIDS Research and Reference Reagent Program , Division of AIDS , NIH/NIAID . Supported by MH63022 , MH072567 , and NS39254 .

Funding

pYK-JRCSF was obtained from the AIDS Research and Reference Reagent Program , Division of AIDS , NIH/NIAID . Supported by MH63022 , MH072567 , and NS39254 .

Funders	Funder number
National Institute of Mental Health	R01MH063022

Keywords

Amyloid beta
Blood-brain barrier
HIV-1
Human brain microvascular endothelial cells
Statins

ASJC Scopus subject areas

Molecular Biology
Cellular and Molecular Neuroscience
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.mcn.2009.11.004

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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 (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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AU - Huang, Wen

AU - Zhong, Yu

AU - Hennig, Bernhard

AU - Toborek, Michal

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N2 - 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.

AB - 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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HIV-1-induced amyloid beta accumulation in brain endothelial cells is attenuated by simvastatin

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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