Metalloproteinases and Brain Arterial Remodeling Among Individuals With and Those Without HIV Infection

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Abstract

Background. This study tests the hypothesis that increased elastolytic activity is associated differentially with dolichoectasia in individuals with and those without human immunodeficiency virus (HIV) infection.

Methods. Large arteries from 84 autopsied brains from HIV-positive individuals and 78 autopsied brains from HIV-negative individuals were stained for metalloproteinase 2 (MMP-2), MMP-3, MMP-9, tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, CD68, and caspase 3. Average pixel intensity was automatically obtained and categorized as high, moderate, or low. Dolichoectasia was defined as a lumen to wall ratio ≥95th percentile.

Results. High MMP-9 staining alone (P = .001) or coexistent with low TIMP-2 staining was associated with dolichoectasia only in HIV-negative individuals (P = <.001). In HIV-positive individuals, MMP-9 was associated with dolichoectasia only when coexpressed with caspase 3 (P = .01). Thinning of the media was associated with CD68 staining (P = <.001) in HIV-negative individuals, while caspase 3 was associated with a thinner media only in HIV-positive individuals (P = .01). Media thickness modified the association between lumen to wall ratio and MMP expression.

Conclusions. A role for MMP/TIMP balance in dolichoectasia appears more prominent in HIV-negative individuals, while apoptosis, mediated by caspase 3, is the most important determinant of media thinning in HIV-infected individuals. Furthermore, apoptosis and media thickness appear to mediate the effects of MMP in the HIV-infected population.

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