Inducible and endothelial nitric oxide synthase genes polymorphism in inflammatory bowel disease

2006 ◽  
Vol 67 (4) ◽  
pp. 326-330 ◽  
Author(s):  
J. Oliver ◽  
M. Gomez-Garcia ◽  
J. R. Vilchez ◽  
M. A. Lopez-Nevot ◽  
A. Pinero ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Bowel Disease ◽  
Nitric Oxide Synthase ◽  
Bowel Disease ◽  
Endothelial Nitric Oxide Synthase ◽  
Inflammatory Bowel ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Influence of the inducible nitric oxide synthase gene (NOS2A) on inflammatory bowel disease susceptibility

2007 ◽  
Vol 59 (11) ◽  
pp. 833-837 ◽  
Author(s):  
M. Carmen Martín ◽  
Alfonso Martinez ◽  
J. Luis Mendoza ◽  
Carlos Taxonera ◽  
Manuel Díaz-Rubio ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Bowel Disease ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Bowel Disease ◽  
Disease Susceptibility ◽  
Inflammatory Bowel ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Increased arginase activity and endothelial dysfunction in human inflammatory bowel disease

2007 ◽  
Vol 292 (5) ◽  
pp. G1323-G1336 ◽  
Author(s):  
Scott Horowitz ◽  
David G. Binion ◽  
Victoria M. Nelson ◽  
Yasmin Kanaa ◽  
Pooria Javadi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Endothelial Cells ◽  
Nitric Oxide Synthase ◽  
Bowel Disease ◽  
No Production ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Oxide Synthase

Nitric oxide (·NO) generation from conversion of l-arginine to citrulline by nitric oxide synthase isoforms plays a critical role in vascular homeostasis. Loss of ·NO is linked to vascular pathophysiology and is decreased in chronically inflamed gut blood vessels in inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis). Mechanisms underlying decreased ·NO production in IBD gut microvessels are not fully characterized. Loss of ·NO generation may result from increased arginase (AR) activity, which enzymatically competes with nitric oxide synthase for the common substrate l-arginine. We characterized AR expression in IBD microvessels and endothelial cells and its contribution to decreased ·NO production. AR expression was assessed in resected gut tissues and human intestinal microvascular endothelial cells (HIMEC). AR expression significantly increased in both ulcerative colitis and Crohn's disease microvessels and submucosal tissues compared with normal. TNF-α/lipopolysaccharide increased AR activity, mRNA and protein expression in HIMEC in a time-dependent fashion. RhoA/ROCK pathway, a negative regulator of ·NO generation in endothelial cells, was examined. The RhoA inhibitor C3 exoenzyme and the ROCK inhibitor Y-27632 both attenuated TNF-α/lipopolysaccharide-induced MAPK activation and blocked AR expression in HIMEC. A significantly higher AR activity and increased RhoA activity were observed in IBD submucosal tissues surrounding microvessels compared with normal control gut tissue. Functionally, inhibition of AR activity decreased leukocyte binding to HIMEC in an adhesion assay. Loss of ·NO production in IBD microvessels is linked to enhanced levels of AR in intestinal endothelial cells exposed to chronic inflammation in vivo.

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