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      Matrix metalloproteinase-2 gene polymorphisms are associated with ischemic stroke in a Hainan population

      research-article
      , MS a , , PhD b , , MS a , , MS a , , MS a , , PhD a ,
      Medicine
      Wolters Kluwer Health
      case-control study, Hainan population, ischemic stroke, MMP

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          Abstract

          Ischemic stroke is a complex vascular disease, which has become 1 of the major causes of morbidity and mortality worldwide. More and more data showed that matrix metalloproteinases (MMPs), in particular, MMP-2 are deleterious after ischaemic stroke. This study investigated the relationship between MMP-2 and stroke risk in the Southern Chinese population.

          We evaluated single nucleotide polymorphisms (SNP) of MMP-2 in stroke patients in an association study using a case-control design. Six SNPs of MMP2 were selected and genotyped by Agena MassARRAY. SNPStats, Haploview was used to analyze genetic data.

          Two SNPs in the MMP-2 gene were significantly associated with stroke risk.

          For rs1132896 (C versus G allele), the C allele was significantly reduced stroke risk (OR = 0.56, 95% confidence intervals [95% CI] = 0.39–0.81, P = .002). The effect of the T allele of rs243849 was IS risk according to an additive genetic model (OR = 0.67, 95% CI = 0.47–0.96, P = .028). We did not found any strong linkage between the six SNPs (rs1132896, rs1053605, rs243849, rs243847, rs243832, rs7201)

          The results presented strongly indicate that MMP-2 genetic variants are an important mediator of stroke risk.

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            Matrix metalloproteinase inhibition prevents oxidative stress-associated blood-brain barrier disruption after transient focal cerebral ischemia.

            Oxidative stress generated during stroke is a critical event leading to blood-brain barrier (BBB) disruption with secondary vasogenic edema and hemorrhagic transformation of infarcted brain tissue, restricting the benefit of thrombolytic reperfusion. In this study, the authors demonstrate that ischemia-reperfusion-induced BBB disruption in mice deficient in copper/zinc-superoxide dismutase (SOD1) was reduced by 88% ( P < 0.0001) and 73% ( P < 0.01), respectively, after 3 and 7 hours of reperfusion occurring after 1 hour of ischemia by the inhibition of matrix metalloproteinases. Accordingly, the authors show that local metalloproteinase-generated proteolytic imbalance is more intense in ischemic regions of SOD1 mice than in wild-type litter mates. Moreover, active in situ proteolysis is, for the first time, demonstrated in ischemic leaking capillaries that produce reactive oxygen species. By showing that oxidative stress mediates BBB disruption through metalloproteinase activation in experimental ischemic stroke, this study provides a new target for future therapeutic strategies to prevent BBB disruption and potentially reperfusion-triggered intracerebral hemorrhage.
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              The paradox of matrix metalloproteinases in infectious disease.

              Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that perform multiple roles in the normal immune response to infection. MMPs facilitate leucocyte recruitment, cytokine and chemokine processing, defensin activation and matrix remodelling. However, excess MMP activity following infection may lead to immunopathology that causes host morbidity or mortality and favours pathogen dissemination or persistence. Here, we review the normal functions of MMPs in immunity and then discuss viral and bacterial infections where excess MMP activity has been implicated in pathology, specifically examining HIV, HTLV-1, hepatitis B, endotoxin shock, Helicobacter pylori and Mycobacterium tuberculosis. Tissue destruction may be exacerbated further by bacterial-derived enzymes which activate the host pro-MMPs. Finally, the potential for therapeutic targeting of excess MMP activity in infection is considered.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                September 2018
                28 September 2018
                : 97
                : 39
                : e12302
                Affiliations
                [a ]Key Laboratory of Resource Biology and Biotechnology in Western China, Northwest University, Ministry of Education, Xi’an, Shaanxi
                [b ]Qingdao Jimo People Hospital, Qingdao, China.
                Author notes
                []Correspondence: Tianbo Jin, #229 North Taibai Road, Xi’an 710069, China (e-mail: jintianbo@ 123456gmail.com ).
                Article
                MD-D-18-02188 12302
                10.1097/MD.0000000000012302
                6181616
                30278505
                464390da-7829-4594-a9dd-b3660de954f4
                Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

                History
                : 28 March 2018
                : 16 August 2018
                Categories
                3500
                Research Article
                Observational Study
                Custom metadata
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                case-control study,hainan population,ischemic stroke,mmp

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