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