Matrix metalloproteinase 10 is associated with disease severity and mortality in patients with peripheral arterial disease

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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“…These observations suggest that MMP-10 is associated with severity and poor outcome in peripheral arterial disease. 117 …”

Section: Special Attributes Of Specific Mmpsmentioning

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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“…Other results suggest that MMP‐10 is associated with severity and poor outcome in peripheral arterial disease. In vivo, MMP‐10 expression has been shown in endothelial cells and macrophages within human atherosclerotic plaques, and augmented MMP‐10 levels have been described in patients with increased thrombin generation, chronic kidney disease, stroke, and diabetes, suggesting a role for MMP‐10 in vascular pathologic processes associated with impaired vascular remodeling and inflammation (Martinez‐Aguilar et al, ). Nonetheless, MMP‐10 is expressed by macrophages and epithelium in response to injury, but its functions in wound repair are unknown.…”

Section: Matrix Metalloproteinase‐10mentioning

confidence: 99%

Intricate Functions of Matrix Metalloproteinases in Physiological and Pathological Conditions

Mittal

Patel

Debs

et al. 2016

Journal Cellular Physiology

143

115

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Matrix metalloproteinases (MMPs) are a diverse group of proteolytic enzymes and play an important role in the degradation and remodeling of the extracellular matrix (ECM). In normal physiological conditions, MMPs are usually minimally expressed. Despite their low expression, MMPs have been implicated in many cellular processes ranging from embryological development to apoptosis. The activity of MMPs is controlled at three different stages: (1) transcription; (2) zymogen activation; and (3) inhibition of active forms by tissue inhibitor metalloproteinases (TIMPs). They can collectively degrade any component of ECM and basement membrane, and their excessive activity has been linked to numerous pathologies mainly including, but not limited to, tumor invasion and metastasis. The lack of information about several MMPs and the steady stream of new discoveries suggest that there is much more to be studied in this field. In particular, there is a need for controlling their expression in disease states. Various studies over the past 30 years have found that each MMP has a specific mode of activation, action, and inhibition. Drugs specifically targeting individual MMPs could revolutionize the treatment of a great number of health conditions and tremendously reduce their burden. In this review article, we have summarized the recent advances in understanding the role of MMPs in physiological and pathological conditions. J. Cell. Physiol. 231: 2599-2621, 2016. © 2016 Wiley Periodicals, Inc.

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“…In addition to enhanced ECM synthesis, vascular mechanical stretch also leads to increased expression of MMPs, such as MMP-2, -3, -9, and -10 [19][20][21]. MMP-2 in particular has been extensively associated with pathological vascular remodeling [5].…”

mentioning

confidence: 99%