Matrix metalloproteinase 9 polymorphisms and systemic lupus erythematosus: correlation with systemic inflammatory markers and oxidative stress

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple organs and is characterized by persistent systemic inflammation. Among the effects of inflammatory mediators, the induction of matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) and oxidative stress has been demonstrated to be important in the development of SLE. In this study, the possible association between MMP-9 and MMP-2 functional promoter polymorphism, stress, and inflammatory markers with development of severe cardiovascular disease (CVD), high blood pressure (HBP), and lupus nephropathy (LN) in SLE patients was investigated. The present case-control study consisted of 109 SLE patients with and without CVD, HBP and LN and 101 gender-and age-matched unrelated healthy controls from a population in western Iran. MMP-2 -G1575A and MMP-9 -C1562T polymorphisms were detected by PCR-RFLP, serum MMP-2 and MMP-9, neopterin, malondialdehyde (MDA) and lipid levels were determined by ELISA, HPLC and enzyme assay, respectively. We found that MMP-9 -C1562 T and MMP-2 -G1575A alleles act synergistically to increase the risk of SLE by 2.98 times (p ¼ 0.015).Findings of this study also demonstrated that there is a significant increase in the serum levels of MMP-2, neopterin and MDA and a significant decrease in serum level of MMP-9 in the presence of MMP-9-C1562 T and MMP-2 -G1575A alleles in SLE patients compared to controls. Further, SLE patients with MMP-9 (C/T þ T/T) genotype had significantly higher serum concentrations of MMP-2, neopterin, MDA and LDL-C, but lower serum MMP-9 and HDL-C levels than corresponding members of the control group. MMP-9 (C/T þ T/T) genotype increased risk of hypertension in SLE patients 2.71-fold. This study for the first time not only suggests that MMP-9 -C1562 T and MMP-2 -G1575A alleles synergistically increase the risk of SLE but also high serum levels of MDA, neopterin, and circulatory levels of MMP-2 and lower MMP-9 in SLE patients. This information may be important in the evaluation of SLE progression and in the elucidation of the mechanisms of the disease pathogenesis. Lupus (2014) 0, 1-9.Key words: Systemic lupus erythematosus; matrix metalloproteinase-2 -C1562T functional promoter; matrix metalloproteinase-9 -C1562T functional promoter; neopterin; malondialdehyde Abbreviations SLE: systemic lupus erythematosus; MMP-2 and MMP-9: matrix metalloproteinases-2 and -9; HBP: high blood pressure; LN: lupus nephropathy; MDA: malondialdehyde; ROS: reactive oxygen species; CAD: coronary artery disease; LDLR: low-density lipoprotein receptor.

Cognitive dysfunction in patients with Systemic Lupus Erythematosus

“…Other antibodies with pathogenic relevance to cognitive dysfunction include anti-cardiolipin antibodies (ACL), anti-neuronal antibodies, anti-endothelial-cell antibodies (AECAs) and anti- Nedd5 C-ter antibodies 8-10. Patients with systemic lupus erythematosus (SLE) who have neuropsychiatric involvement were found to have significantly higher levels of matrix metalloproteinase-9 (MMP-9) in their serum and in cerebrospinal fluid (CSF), as compared to those without neuropsychiatric syndromes 11,12…”

Matrix metalloproteinase gene polymorphisms and susceptibility to systemic sclerosis

“…MMP genetic polymorphisms and levels of gene expression have been associated with several diseases, including chronic obstructive pulmonary disease, coronary heart disease, rheumatoid arthritis, and systemic lupus erythematosus (Schirmer et al, 2009;Scherer et al, 2010;Bahrehmand et al, 2015;Jiang et al, 2016;Ma et al, 2015Ma et al, , 2016. Different studies have addressed the MMP serum levels and MMP gene expression in SSc (Young-Min et al, 2001;Kikuchi et al, 2002;Toubi et al, 2002;Meng et al, 2008;Brown et al, 2012;Frost et al, 2012).…”

Matrix metalloproteinase‐9, 10, and stress hyperglycaemia in acute kidney injury

“…Matrix metalloproteinase (MMP)-10 levels are known to be associated with severe atherosclerosis in patients with CKD and therefore could be used as a novel indicator. 6,7,28 Thus, MMP-9 could serve as an inflammatory marker, and MMP inhibitors may be used in the treatment of acute infections in geriatric patients. 24 We did not find any significant relation between MMP-9 levels and prognosis.…”

“…26 Ma et al 27 showed the importance of inflammation in cardiac ageing and the role of MMP-9 in the direct and indirect polarization of the macrophages. Bahrehmond et al 28 found a correlation between MMP-9 and systemic inflammatory markers and oxidative stress in patients with systemic lupus erythematosus. Vondooren et al 29 stated that MMP inhibitors could be used in acute neurologic inflammation due to their known role in monomeric and multimeric forms in central nervous system infection and inflammation.…”

“…Many studies have indicated MMP-9 to be a biomarker associated with inflammatory mediators and inflammatory diseases. 6,7,28 Thus, MMP-9 could serve as an inflammatory marker, and MMP inhibitors may be used in the treatment of acute infections in geriatric patients.…”