Skip Navigation

Publication Detail

Title: HIV-1 Tat-induced cerebrovascular toxicity is enhanced in mice with amyloid deposits.

Authors: Chen, Lei; Choi, Jeong June; Choi, Yean Jung; Hennig, Bernhard; Toborek, Michal

Published In Neurobiol Aging, (2012 Aug)

Abstract: HIV-1-infected brains are characterized by elevated depositions of amyloid beta (Aýý); however, the interactions between Aýý and HIV-1 are poorly understood. In the present study, we administered specific HIV-1 protein Tat into the cerebral vasculature of 50-52-week-old double transgenic (B6C3-Tg) mice that express a chimeric mouse/human amyloid precursor protein (Mo/HuAPP695swe) and a mutant human presenilin 1 (PS1-dE9) and are characterized by increased Aýý depositions in the brain. Exposure to Tat increased permeability across cerebral capillaries, enhanced disruption of zonula occludens (ZO)-1 tight junction protein, and elevated brain expression of matrix metalloproteinase-9 (MMP-9) in B6C3-Tg mice as compared with age-matched littermate controls. These changes were associated with increased leukocyte attachment and their transcapillary migration. The majority of Tat-induced effects were attenuated by treatment with a specific Rho inhibitor, hydroxyfasudil. The results of animal experiments were reproduced in cultured brain endothelial cells exposed to Aýý and/or Tat. The present data indicate that increased brain levels of Aýý can enhance vascular toxicity and proinflammatory responses induced by HIV-1 protein Tat.

PubMed ID: 21764480 Exiting the NIEHS site

MeSH Terms: Amyloid beta-Peptides/metabolism*; Animals; Cerebral Arteries/drug effects; Cerebral Arteries/physiopathology; Cerebrovascular Disorders/chemically induced*; Cerebrovascular Disorders/physiopathology*; Gene Products, tat/toxicity*; Mice; Mice, Transgenic; Plaque, Amyloid/metabolism*; Vasculitis/chemically induced*; Vasculitis/physiopathology*

Back
to Top