Inducible nitric oxide synthase is present in human abdominal aortic aneurysm and promotes oxidative vascular injury.
OBJECTIVE
Nitric oxide (NO), catalyzed by inducible NO synthase (iNOS), may be important in the pathophysiologic characteristics of many vascular diseases. Although there is indirect evidence to support the presence of iNOS in abdominal aortic aneurysm (AAA) in human beings, no definitive study has confirm this finding. The present study was designed to assess expression of iNOS in AAA in human beings. Furthermore, the activity of iNOS and the oxidative vascular injury initiated by iNOS were assessed with detection of nitrotyrosine, which is a marker indicative of formation and activity of the NO-derived oxidant peroxynitrite.


METHODS
We studied 25 patients with AAA and 10 patients with normal abdominal aortas. In situ hybridization and immunohistochemistry were used in tissue sections to localize iNOS messenger RNA (mRNA) and protein. Double staining with a combination of in situ hybridization and immunohistochemistry was used to simultaneously demonstrate iNOS mRNA expression and its cellular localization. The presence of peroxynitrite was indirectly assessed with immunostaining with anti-nitrotyrosine antibodies.


RESULTS
In situ hybridization and immunohistochemistry confirmed the presence of iNOS in media and adventitia of AAA in all 25 patients. Specific cell markers identified iNOS mRNA-positive cells mainly as T and B lymphocytes, macrophages, and smooth muscle cells. Positive immunostaining for nitrotyrosine was present in macrophages and smooth muscle cells. Normal abdominal aorta demonstrated virtually no iNOS or nitrotyrosine expression.


CONCLUSIONS
Stimulated expression of iNOS is associated with degeneration of AAA in human beings, and the activity of this enzyme under such conditions preferentially promotes formation and activity of peroxynitrite and further contributes to oxidative tissue and cellular injury in AAA. This may be important in the pathogenesis of AAA.
Zhang
Jian
J
Third General Surgery Department, First Affiliated Hospital, China Medical University, Shenyang 110001, China. jianzhang_cmu@yahoo.com.cn
Schmidt
Jan
J
Ryschich
Eduard
E
Mueller-Schilling
Martina
M
Schumacher
Hardy
H
Allenberg
Jens Rainer
JR
D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress / Q000502:physiology*; D030421:Peroxynitrous Acid / Q000378:metabolism
D030421:Peroxynitrous Acid; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II