title: Tumor necrosis factor alpha is a key modulator of inflammation in cerebral aneurysms.
abstract: OBJECTIVE
  Although intracranial aneurysms (IAs) are a major public health problem in the United States, few etiological factors are known. Most aneurysms remain asymptomatic until they rupture, producing subarachnoid hemorrhage, one of the most severe forms of stroke. Despite the technical advances in endovascular and microsurgical treatment, these patients still have high mortality and morbidity rates. Hence, the biology of aneurysm formation and growth is of intense interest. The presence of T and B lymphocytes, as well as macrophages, in human IA tissues suggests a role for inflammation in IA pathogenesis. However, the types of cytokines that are involved and regulated during cerebral aneurysm formation and growth are not known. To study the underlying pathogenesis of IA, we analyzed the expression of cytokines that participate in proinflammatory and anti-inflammatory responses.
  
  
  METHODS
  Polymerase chain reaction was used to assess relative messenger ribonucleic acid expression levels of cytokines and an apoptotic modulator, Fas-associated death domain protein. Western blot analysis was used to determine protein expression from these genes.
  
  
  RESULTS
  We show that the proinflammatory cytokine, tumor necrosis factor alpha and its proapoptotic downstream target, Fas-associated death domain protein, are increased in human aneurysms. In contrast, interleukin 10, which is secreted predominantly by T helper 2 cells, was absent in aneurysms. Polymerase chain reaction-derived gene expression data were confirmed by Western blotting using specific antibodies.
  
  
  CONCLUSIONS
  Increased tumor necrosis factor alpha and Fas-associated death domain protein may have deleterious primary and secondary effects on cerebral arteries by promoting inflammation and subsequent apoptosis in vascular and immune cells, thereby weakening vessel walls.
authors.affiliation: St. Luke's Roosevelt Hospital Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York, USA. tj56@columbia.edu
authors.forename: Thottala
authors.initials: T
authors.lastname: Jayaraman
authors.forename: Vanessa
authors.initials: V
authors.lastname: Berenstein
authors.forename: Xiaguai
authors.initials: X
authors.lastname: Li
authors.forename: Jillian
authors.initials: J
authors.lastname: Mayer
authors.forename: Michael
authors.initials: M
authors.lastname: Silane
authors.forename: Yang Sam
authors.initials: YS
authors.lastname: Shin
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Niimi
authors.forename: Türker
authors.initials: T
authors.lastname: Kiliç
authors.forename: Murat
authors.initials: M
authors.lastname: Gunel
authors.forename: Alejandro
authors.initials: A
authors.lastname: Berenstein
mesh_terms: D000328:Adult; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism*; D002532:Intracranial Aneurysm / Q000150:complications* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D029681:Arabidopsis Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D044943:Fatty Acid Desaturases; C084083:Fad7 protein, Arabidopsis