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Metalloproteinases and brain arterial remodeling with and without HIV.

Metalloproteinases and brain arterial remodeling with and without HIV.
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Gutierrez J, Menshawy K, Goldman J, Dwork AJ, Elkind MS, Marshall RS, Morgello S,


Gutierrez J, Menshawy K, Goldman J, Dwork AJ, Elkind MS, Marshall RS, Morgello S, (click to view)

Gutierrez J, Menshawy K, Goldman J, Dwork AJ, Elkind MS, Marshall RS, Morgello S,

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The Journal of infectious diseases 2016 8 22() pii

Abstract
BACKGROUND
 To test the hypothesis that increased elastolytic activity would be associated differentially with dolichoectasia in individuals with and without HIV.

METHODS
 Brain large arteries were obtained from 84 HIV+ and 78 HIV- autopsies and stained for metalloproteinase (MMP)-2, MMP-3, MMP-9, tissue inhibitor of metalloproteinases (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≥95(th) percentile.

RESULTS
 High MMP-9 staining alone (P=0.001) or coexisting with low TIMP-2 staining, was associated with dolichoectasia only in HIV- individuals (P=<0.001). In HIV+ individuals, MMP-9 was associated with dolichoectasia only when co-expressed with caspase-3 (P=0.01). Thinning of the media was associated with CD68 staining (P=<0.001) in HIV- individuals while caspase-3 was associated with a thinner media only in HIV+ individuals (P=0.01). Media thickness modified the association between lumen-to-wall ratio and MMP expression. CONCLUSION
 A role for MMP/TIMP balance in dolichoectasia appears more prominent in HIV- individuals, while apoptosis, mediated by caspase-3, is the most important determinant of media thinning in HIV. Furthermore, apoptosis and media thickness appear to mediate the effects of MMP in the HIV population.

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