title: Metalloproteinases and Brain Arterial Remodeling Among Individuals With and Those Without HIV Infection.
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.
authors.affiliation: Department of Neurology.
authors.forename: Jose
authors.initials: J
authors.lastname: Gutierrez
authors.affiliation: Alexandria Faculty of Medicine, Alexandria University, Egypt.
authors.forename: Khaled
authors.initials: K
authors.lastname: Menshawy
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons.
authors.forename: James
authors.initials: J
authors.lastname: Goldman
authors.affiliation: Department of Pathology and Cell Biology, College of Physicians and Surgeons.|Department of Psychiatry, Columbia University Medical Center.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dwork
authors.affiliation: Department of Neurology.|Department of Epidemiology, Mailman School of Public Health, Columbia University.
authors.forename: Mitchell S V
authors.initials: MS
authors.lastname: Elkind
authors.affiliation: Department of Neurology.
authors.forename: Randolph S
authors.initials: RS
authors.lastname: Marshall
authors.affiliation: Departments of Neurology, Neuroscience, and Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001158:Arteries / Q000378:metabolism* / Q000503:physiopathology*; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology*; D053148:Caspase 3 / Q000378:metabolism; D005260:Female; D015658:HIV Infections / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D053148:Caspase 3; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human
keywords: HIV; brain; dolichoectasia; histopathology; remodeling