title: Variations in structural protein expression and endothelial cell proliferation in relation to clinical manifestations of cerebral cavernous malformations.
abstract: OBJECTIVE
  Cerebral cavernous malformations (CCMs) are associated with hemorrhagic proliferation of endothelial-lined vascular caverns, resulting in hemorrhagic stroke, epilepsy, and other neurological manifestations. We hypothesize that structural protein expression and endothelial cell proliferation markers within CCM lesions are different in the setting of various clinical manifestations.
  
  
  METHODS
  The percentage of immunohistochemically stained caverns positive for collagen IV, fibronectin, laminin, alpha-smooth muscle actin, myosin, and smoothelin and the percentage of dividing endothelial cells within caverns were determined in 36 excised CCM surgical specimens. These were compared in CCMs with different multiplicity, location, and size in patients of different age, sex, seizure status, and hemorrhage status.
  
  
  RESULTS
  Comparisons of seven lesion features and clinical manifestations with the fraction of caverns containing the structural proteins studied and endothelial cell proliferation demonstrated no significant differences. A possible exception was the difference (P < 0.05) in the fraction (mean +/- standard deviation) of positively stained caverns for collagen IV between adult (0.63 +/- 0.39) and pediatric patients (0.87 +/- 0.21) as well as fewer caverns with laminin expression in older patients. These trends did not sustain significance with Bonferroni's correction for multiple comparisons.
  
  
  CONCLUSIONS
  The fraction of caverns containing the particular structural proteins studied and endothelial cell proliferation within caverns are not correlated with particular lesion features and clinical manifestations that were investigated in CCMs. The possible fewer fractions of caverns containing collagen IV and laminin in adult lesions compared with pediatric lesions may have implications for lesion regression and quiescence with age.
authors.affiliation: Department of Neurosurgery, Northwestern University Feinberg School of Medicine, Evanston Northwestern Healthcare, Evanston, Illinois, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Shenkar
authors.forename: Hemant
authors.initials: H
authors.lastname: Sarin
authors.forename: Nabil A
authors.initials: NA
authors.lastname: Awadallah
authors.forename: Judith
authors.initials: J
authors.lastname: Gault
authors.forename: Bette K
authors.initials: BK
authors.lastname: Kleinschmidt-DeMasters
authors.forename: Issam A
authors.initials: IA
authors.lastname: Awad
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000293:Adolescent; D000328:Adult; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000096:biosynthesis; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D042783:Endothelial Cells; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D005353:Fibronectins / Q000096:biosynthesis; D006801:Humans; D007223:Infant; D002538:Intracranial Arteriovenous Malformations / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D019394:Ki-67 Antigen / Q000096:biosynthesis; D007797:Laminin / Q000096:biosynthesis; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis; D009218:Myosins / Q000096:biosynthesis
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; D005353:Fibronectins; D019394:Ki-67 Antigen; D007797:Laminin; D009124:Muscle Proteins; C100762:SMTN protein, human; D003094:Collagen; D009218:Myosins