NITRO-OXIDATIVE STRESS, VEGF AND MMP-9 IN PATIENTS WITH CIRRHOTIC AND NON-CIRRHOTIC PORTAL HYPERTENSION

Abstract

Background and aims. Nitro-oxidative stress may have pathophysiological
consequences. The study aimed to assess the nitro-oxidative stress, the vascular growth
factor, and metalloproteinase-9 levels in patients with noncirrohic and cirrhotic portal
hypertension.
Methods. Patients with noncirrhotic portal hypertension (n=50) and cirrhotic
portal hypertension (n=50) from the 3rd Medical Clinic in Cluj-Napoca Romania were
prospectively enrolled between October 2004 and October 2006. A control group of
healthy volunteers (n=50) was also evaluated. Nitro-oxidative stress was assessed by
measuring serum concentration of nitrites and nitrate, 3-nitrotyrosine, total oxidative
status, total antioxidant reactivity, and oxidative stress index. Serum vascular growth
factor and matrix metalloproteinase-9 were also determined.
Results. Serum nitrites and nitrate levels significantly increased in both
noncirrhotic (p<0.001) and cirrhotic portal hypertension (p=0.057). 3-nitrotyrosine
also increased in noncirrhotic (p=0.001) and cirrhotic portal hypertension patients
(p=0.014). Total oxidative status showed a significant increase in noncirrhotic (p<0.001)
and in cirrhotic portal hypertension (p<0.001), but total antioxidant reactivity did not change
significantly. The oxidative stress index increased in both noncirrhotic (p <0.001) and cirrhotic
portal hypertension (p<0.001), as well as the serum vascular growth factor (p=0.005 and
p=0.01, respectively). In NCPHT patients serum MMP-9 was significantly lower than in
the healthy controls (p=0.03) and CPHT patients (p=0.05).
Conclusion. In patients with noncirrhotic and cirrhotic portal hypertension a
significant systemic nitro-oxidative stress was found, correlated with an increase of
VEGF. MMP-9 decreased in noncirrhotic portal hypertension.