Implication of oxidative stress and its correlation with activity of matrix metalloproteinases in patients with Takayasu's arteritis disease

Abstract

Oxidative stress and activation of matrix metalloproteinases (MMPs) together have been widely implicated in various inflammatory vascular disorders. As Takayasu's arteritis (TA) is an inflammatory disorder characterized by destruction of elastic fibers, we hypothesized that oxidative stress and MMPs might play an important role in pathophysiology of the disease. 40 patients with clinically defined TA and equal number of normal, healthy, controls were enrolled in the study. Subjects with TA were further divided into clinically active disease or in remission phase of the disease. Augmented levels of 8-isoPGF(2α) (238.9±125.7 vs 79.5±29.1 ng/ml), nitrite (NO(2)(-)) (14.9±15.6 vs 3.3±1.7 μM) were observed in TA patients as compared to the controls (p<0.01). Further, 8-iso-PGF(2α) (272.2±117.3 vs 105.9±43.5 ng/ml) and NO(2)(-) (17.9±16.1 vs 3.1±2.5 μM) levels were higher in subjects with active disease vs those in remission (p<0.05). Zymography pattern revealed two bands in the range of 85-92 kDa (MMP-9) and 65-72 kDa (MMP-2). Total gelatinolytic activity was found to be significantly higher in subjects with TA as compared to the controls (p<0.05). Gelatinolytic activity was moderately low in controls and subjects in remission as compared to those with active disease (p>0.05). Further, gelatinolytic activity showed a positive correlation with 8-iso-PGF(2α) and NO levels in patients with TA. Increased oxidative stress and MMP activity may play an active role in the progression of Takayasu's arteritis disease.