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

doi:10.1016/j.ijcard.2009.09.557

International Journal of Cardiology

Volume 145, Issue 2, 19 November 2010, Pages 286-288

https://doi.org/10.1016/j.ijcard.2009.09.557 Get rights and content

Abstract

Background

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.

Methods

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.

Results

Augmented levels of 8-isoPGF_2α (238.9 ± 125.7 vs 79.5 ± 29.1 ng/ml), nitrite (NO₂⁻) (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 NO₂⁻ (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.

Conclusions

Increased oxidative stress and MMP activity may play an active role in the progression of Takayasu's arteritis disease.

Introduction

The aetiopathogenesis of Takayasu's arteritis (TA) disease remains enigmatic and various mechanisms such as post-infective, autoimmune, ethnic susceptibility and a genetic predisposition have been postulated [1]. The diagnosis of this disease is difficult, because only non-specific symptoms may be present during the early phase of TA, symptoms of arterial stenosis and occlusion are late phase manifestations and the current diagnostic criteria focus mainly on these manifestations [2]. The disease tends to progress despite treatment with glucocorticoid/immunosuppressive agents and selection of an appropriate therapeutic strategy is based on monitoring the severity of the disease [3], [4].

Oxidative stress is a cardinal feature of the inflammatory process and has been generally considered to be uniformly deleterious in vascular abnormalities. An obvious mechanism of oxidative stress (e.g. in the form of reactive oxygen species (ROS) and reactive nitrosative species (RNS)) is through oxidative damage to cellular proteins, membranes and DNA [5], [6]. Another mechanism is the potential of ROS and RNS to influence extracellular matrix remodeling through activation of matrix metalloproteinases (MMPs) [5], [6]. 8-isoprostaglandin F_2α (8-iso-PGF_2α) has been shown to be a sensitive and specific biomarker of the oxidative stress in vivo and is a member of isoprostane family which have been shown to exert potent biological actions [5], [7].

Though, deeply explored in other diseases, the degree of oxidative stress and its relation to Takayasu's arteritis is unclear. Also, how oxidative stress and MMP activity are linked together in the aetiopathogenesis of TA disease is not known. The aim of the present study is to investigate whether oxidative stress indices i.e. (8-iso-PGF_2α and NO₂⁻) and MMP activity could correlate with the disease activity.

Section snippets

Materials and methods

40 patients with angiographically proven Takayasu's arteritis (Group I) and 40 normal healthy controls (Group II) were enrolled in the present study as described earlier [8]. The study has been approved by The Institutional Ethics Committee.

Plasma 8-iso-PGF_2α was determined in all the study subjects using commercially available immunoassay kit (Assay Designs, USA). Plasma nitrite (NO₂⁻), as a stable end product of NO production and DNA damage was determined as described previously [9]. Gelatin

Results

The baseline characteristics of the subjects are shown in Table 1. We observed no significant difference between the two study groups as far as lipid and lipoprotein profile, blood urea, serum creatinine and uric acid levels are concerned (p > 0.05; data not shown). Levels of 8-iso-PGF_2α and NO₂⁻ were found to be significantly higher in patients with TA as compared to the normal healthy subjects (p < 0.01). Further, we also observed higher levels of 8-iso-PGF_2α and NO₂⁻ in TA patients with active

Discussion

Takayasu's arteritis (TA) is a progressive inflammatory and occlusive disease of the unknown origin and mainly affects the aorta and its branches, as well as the pulmonary and coronary arteries [2]. However, the current focus of the research is on newer developments which have taken place with regard to etiology, diagnosis of disease activity and management aspects.

Augmented levels of 8-isoPGF_2α in TA patients reflects enhanced lipid peroxidation which may possibly be due to an acute

Acknowledgements

The authors thank the Indian Council of Medical Research (ICMR), New Delhi for research funding. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [20].

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Letter to the EditorImplication of oxidative stress and its correlation with activity of matrix metalloproteinases in patients with Takayasu's arteritis disease

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Materials and methods

Results

Discussion

Acknowledgements

Eur J Vasc Endovasc Surg

J Am Coll Cardiol

Int J Cardiol

Trends Endocrinol Metab

Int J Cardiol

Clin Chim Acta

Int J Cardiol

Isoprostanes: markers and mediators of oxidative stress

FESEB J

The nitrosative–oxidative disequilibrium hypothesis on the pathogenesis of cardiovascular disease

FEBS J

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