Tumor necrosis factor alpha is a key modulator of inflammation in cerebral aneurysms.
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.
Jayaraman
Thottala
T
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
Berenstein
Vanessa
V
Li
Xiaguai
X
Mayer
Jillian
J
Silane
Michael
M
Shin
Yang Sam
YS
Niimi
Yasunari
Y
Kiliç
Türker
T
Gunel
Murat
M
Berenstein
Alejandro
A
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*
D029681:Arabidopsis Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D044943:Fatty Acid Desaturases; C084083:Fad7 protein, Arabidopsis