The Role of Matrix Metalloproteinase Polymorphisms in Ischemic Stroke

Chang, Jason J.; Stanfill, Ansley Grimes; Pourmotabbed, Tayebeh

doi:10.3390/ijms17081323

Cited by 43 publications

(57 citation statements)

References 114 publications

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“…Polymorphisms in the MMP genes can be influenced by racial and ethnic background., and could ultimately affect the presentation of ischemic stroke. 52 MMPs also play key roles in the spread of viral infection, inflammation and remodeling of the respiratory airways and tissue fibrosis. 53 MMPs may also participate in cancer development, progression, invasiveness and dissemination by promoting a pro-tumorigenic microenvironment and modulating the cell-ECM and cell-to-cell contacts.…”

Section: Mmps Ecm Degradation and Tissue Remodelingmentioning

confidence: 99%

Biochemical and Biological Attributes of Matrix Metalloproteinases

Cui

Khalil

2017

Progress in Molecular Biology and Translational Science

941

891

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Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are involved in the degradation of various proteins in the extracellular matrix (ECM). Typically, MMPs have a propeptide sequence, a catalytic metalloproteinase domain with catalytic zinc, a hinge region or linker peptide, and a hemopexin domain. MMPs are commonly classified on the basis of their substrates and the organization of their structural domains into collagenases, gelatinases, stromelysins, matrilysins, membrane-type (MT)-MMPs, and other MMPs. MMPs are secreted by many cells including fibroblasts, vascular smooth muscle (VSM) and leukocytes. MMPs are regulated at the level of mRNA expression and by activation of their latent zymogen form. MMPs are often secreted as inactive proMMP form which is cleaved to the active form by various proteinases including other MMPs. MMPs cause degradation of ECM proteins such as collagen and elastin, but could influence endothelial cell function as well as VSM cell migration, proliferation, Ca2+ signaling and contraction. MMPs play a role in tissue remodeling during various physiological processes such as angiogenesis, embryogenesis, morphogenesis and wound repair, as well as in pathological conditions such as myocardial infarction, fibrotic disorders, osteoarthritis, and cancer. Increases in specific MMPs could play a role in arterial remodeling, aneurysm formation, venous dilation and lower extremity venous disorders. MMPs also play a major role in leukocyte infiltration and tissue inflammation. MMPs have been detected in cancer, and elevated MMP levels have been associated with tumor progression and invasiveness. MMPs can be regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs), and the MMP/TIMP ratio often determines the extent of ECM protein degradation and tissue remodeling. MMPs have been proposed as biomarkers for numerous pathological conditions and are being examined as potential therapeutic targets in various cardiovascular and musculoskeletal disorders as well as cancer.

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Section: Mmps Ecm Degradation and Tissue Remodelingmentioning

confidence: 99%

Biochemical and Biological Attributes of Matrix Metalloproteinases

Cui

Khalil

2017

Progress in Molecular Biology and Translational Science

941

891

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show abstract

“…Expression and activity of matrix metalloproteinases (MMPs) are induced in reaction to inflammatory response. The largest alleles, (CA) >21 , of MMP9 promoter polymorphism, have been associated with expression alterations, mainly, in advanced atherosclerotic lesions [10,11]. Regarding reactive oxygen species (ROS), nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), is a crucial regulator of vascular homeostasis and a potent antiatherogenic and antithrombotic [12,13].…”

Section: Introductionmentioning

confidence: 99%

ALOX5,LPA,MMP9andTPOgene polymorphisms increase atherothrombosis susceptibility in middle-aged Mexicans

et al. 2020

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Atherothrombosis is the cornerstone of cardiovascular diseases and the primary cause of death worldwide. Genetic contribution to disturbances in lipid metabolism, coagulation, inflammation and oxidative stress increase the susceptibility to its development and progression. Given its multifactorial nature, the multiloci studies have been proposed as potential predictors of susceptibility. A cross-sectional study was conducted to explore the contribution of nine genes involved in oxidative stress, inflammatory and thrombotic processes in 204 subjects with atherothrombosis matched by age and gender with a healthy group ( n = 204). To evaluate the possibility of spurious associations owing to the Mexican population genetic heterogeneity as well as its ancestral origins, 300 unrelated mestizo individuals and 329 Native Americans were also included. ALOX5 , LPA , MMP9 and TPO gene polymorphisms, as well as their multiallelic combinations, were twice to four times more frequent in those individuals with clinical manifestations of atherothrombosis than in the healthy group. Once adjusting for population stratification was done, these differences remained. Our results add further evidence on the contribution of ALOX5 , LPA , MMP9 and TPO polymorphisms to atherothrombosis development in the middle-aged group, emphasizing the multiethnic studies in search of gene risk polymorphisms.

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“…It has capacity to digest basement membrane components, such as elastin, laminin, fibronectin and other substrates, and also play a synergistically activating role with other pathogenetic MMPs. Therefore, MMP12 plays a role in the aortic wall destruction and aneurysm development . MMP12rs2276109 polymorphism in promoter region involving the substitution A/G is responsible for gene transcriptional activity.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, MMP12 plays a role in the aortic wall destruction and aneurysm development. 48,65 MMP12rs2276109 polymorphism in promoter region involving the substitution A/G is responsible for gene transcriptional activity. The A allele of MMP12rs2276109 has been investigated to be associated with the higher expression level of MMP12.…”

Section: The Mmp12 Polymorphismsmentioning

confidence: 99%

Matrix metalloproteinase family polymorphisms and the risk of aortic aneurysmal diseases: A systematic review and meta‐analysis

Tan¹,

Lv²,

Jun

et al. 2017

Clinical Genetics

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It has been suggested that matrix metalloproteinase (MMP) polymorphisms are associated with the pathogenesis of aortic aneurysmal diseases. In this study, we conducted a systematic review with an update meta-analysis to investigate the relationship between MMP family polymorphisms and aortic aneurysmal diseases. We systematically reviewed 24 polymorphisms in 8 MMP genes related to the risk of abdominal aortic aneurysm (AAA), thoracic AA or thoracic aortic dissection (TAD). A total of 19 case-control studies with 15 highly studied MMP polymorphisms were included in our meta-analysis. Our results suggested that MMP2rs243865,

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The Role of Matrix Metalloproteinase Polymorphisms in Ischemic Stroke

Cited by 43 publications

References 114 publications

Biochemical and Biological Attributes of Matrix Metalloproteinases

Biochemical and Biological Attributes of Matrix Metalloproteinases

ALOX5,LPA,MMP9andTPOgene polymorphisms increase atherothrombosis susceptibility in middle-aged Mexicans

Matrix metalloproteinase family polymorphisms and the risk of aortic aneurysmal diseases: A systematic review and meta‐analysis

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