Matrix Metalloproteinases and Their Inhibitors and Mmp3 Polymorphism in Peripheral Vascular Disease

Peripheral Vascular Disease (PVD) is a progressive and chronic disease resulting from atherosclerotic events. Atherosclerotic obstructions are consequence of chronic ischemia in the lower extremity arteries in patients with PVD. It is suggested that blood levels of Matrix Metalloproteinases (MMPs) and endogenous Tissue inhibitors of Metalloproteinases (TIMPs) have been associated with atherosclerosis. In this study, we aimed to demonstrate whether or not levels of MMPs and TIMPs and genetic variations in the matrixmetalloproteinase 3 (MMP3) 1171 5A/6A play a role in PVD. The study included 102 patients with PVD and 65 healthy controls. Serum MMPs and TIMPs level were determined by using ELISA method. Genotype analysis was performed for MMP3 -1171 5A/6A polymorphism in samples from peripheral blood. Polimerase chain reaction (PCR) was performed in DNA samples and then digested amplified DNA with Tth111 I enzyme by using Restriction fragment length polymophism (RFLP). We found that MMP-2 (p<0.001), MMP-9 (p<0.001) and TIMP-1 (p<0.01), TIMP-2 (p<0.001) levels in serum were significantly higher in patients with PVD as compared to the those of control group. In PVD group, We found the ratios of MMP-2/TIMP2 and MMP-9/TIMP-2 were increased in PVD group than those of controls (for both p<0.001). In addition, Pearson’s correlation test was performed between MMPs and TIMPs levels in patients with PVD group. We found lineer correlation between MMP-2 and TIMP-2 (r=0.504 p=0.000), and TIMP-1 (r=0.297 p=0.002). In contrast, we found reverse correlation between MMP-2 and MMP-9 (r=-0.504 p=0.000). The 5A5A, 6A5A genotypes of MMP3 -1171 5A/6A were more frequent in patients with PVD than in controls. In contrast, 6A6A genotype (p<0.001) and 6A allele (p<0.001) were significantly decreased in patients as compared with controls. Our results showed that the changes in the levels of MMPs, TIMPs and the ratios of MMP-2/TIMP2 and MMP-9/TIMP-2 in serum and 6A6A genotype of MMP3 -1171 5A/6A are important in progression of PVD. Keywords-MMP; TIMP; PVD; polymorphism INTRODUCTION Peripheral vascular disease (PVD) is an chronic and an atherosclerotic procesess. It is consequence of chronic ischemia seen in the lower extremity arteries. MMP’s are associated with vascular remodelling and regulating of angiogenesis that is a formation of new vessels in atherosclerotic proceseses. In appropriate remodeling underlies the pathogenesis of major cardiovascular disease such as atherosclerosis. Matrix Metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) are key modulators of ECM turnover. The alterations in the synthesis and/or degradation of the arterial ECM have been associated with vascular disease. Recently it has been shown that the increased expression of MMPs and their contribution to weakening of the vascular wall by degrading the ECM is an important factor progressing of atherosclerotic procesess. Increased levels of the specialized enzymes called MMPs and their inhibitors TIMPs have been reported in patients with PVD. Moreover, it has been suggestedthat both MMPs and TIMPs play an important role in the pathological remodelling of ECM in PVD. MMP3 genotype possibly could be an important factor in regulation of the ECM in PVD. In the light of these findings, we aimed to demonstrate whether or not levels of MMPs and TIMPs are important factors in PVD. On the other hand, we investigated whether the genetic variations in the MMP3 -1171 5A/6A are contribution to progression of PVD. Materials and Methods The study included 102 patients with PVD (age: 62.78 ± 11.54) and 65 healthy controls (age: 59.66 ± 10.36). The study group were composed from patients which enrolled to the Department of General Surgery, Istanbul University, Istanbul Faculty of Medicine. The exclusion criteria for the control group were included obvious symptoms or signs of PAD who have an ankle-brachial index lower than 0.9 on clinical assessment. Patients with co-existing renal impairment, pernicious anemia, hypothyroidism, malignancy and patients taking medications such as thiazide diuretics were excluded from the study. The control group were consisted of healthy adults who had any accompanying disease such as hyperlipidemia, International Scientific Journal Medical and Biological Sciences http://bioscience.scientific-journal.com