Matrix Metalloproteinases and Atherogenesis in Dependence of Age

Kunz, J

doi:10.1159/000096351

Cited by 30 publications

(16 citation statements)

References 247 publications

(135 reference statements)

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“…18 MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, and MMP-13 are the recently identified macrophages MMPs. 51,[473][474][475][476][477] MMPs are regulated by cytokines and mechanical strain 478 and they exert their effect on the ECM components, including collagen, elastin, and proteoglycans. 51 MMPs are activated and also activate other macrophage proteases especially urokinase (via plasmin).…”

Section: M a C R O P H A G E S I N P L A Q U E R U P T U R E A N D mentioning

confidence: 99%

Macrophages: An elusive yet emerging therapeutic target of atherosclerosis

Tiwari

Singh

Barthwal

2007

Medicinal Research Reviews

139

120

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Macrophages are central to the initiation and progression of atherosclerosis and thus can be very appropriate targets for therapy. Cell adhesion molecules mediating monocytes recruitment to the endothelium are attractive therapy targets and their inhibitors are in clinical trials. Macrophage scavenger receptors like SR-A and CD-36 mediate foam cell formation by facilitating the uptake of modified lipids. Peroxisome proliferator-activated receptors (PPAR), liver X receptor (LXR)-mediated signaling, mitogen-activated protein kinase (MAPK) induced phosphorylation events seem to play an important role in this phenomenon. Proteins affecting macrophage cholesterol metabolism and transport, including ATP-binding cassette (ABC) A1, ABCG1, acylCoA:cholesterol acyltransferase (ACAT), apolipoprotein A-1 (ApoA-1), neutral cholesteryl ester hydrolase (NCEH) also regulate foam cell formation and are being developed as therapeutic targets by many pharmaceutical companies. Macrophage proliferation and apoptosis are important events controlling inflammatory response, plaque vulnerability, and destabilization. Free cholesterol (FC) activates the macrophage endoplasmic reticulum (ER) stress pathway and apoptosis. Free radicals and nitric oxide also modulate macrophage foam cell formation and apoptosis. Various antioxidants like AGI-1067 and BO-653 are in clinical trials for atherosclerosis treatment. Macrophage matrix metalloproteinase's (MMP's) play a significant role in weakening and rupture of plaques. Efforts are on to develop isoform specific MMP inhibitor. CD-14, MMP-3, ABCA1, Toll-like receptor-4 (TLR-4), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), arachidonate lipoxygenase-15 (ALOX-15), and Connexin37 polymorphisms and macrophage dysfunction signify their importance in atherosclerosis. Deciphering the role of macrophages in regulating dyslipidemia and inflammation during atherosclerosis is important for developing them as therapeutic targets. ß 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 4, 483-544, 2008

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Section: M a C R O P H A G E S I N P L A Q U E R U P T U R E A N D mentioning

confidence: 99%

Macrophages: An elusive yet emerging therapeutic target of atherosclerosis

Tiwari

Singh

Barthwal

2007

Medicinal Research Reviews

139

120

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“…Genetic polymorphisms may, for example, affect MMP expression levels by conferring protection or propensity to vulnerable plaques [52][53][54]. Moreover, studies using MMP gene knockout mice have indicated that MMP-2 and MMP-9 play key roles in cardiac rupture after myocardial infarction [55,56].…”

Section: Introductionmentioning

confidence: 99%

Metalloproteinases and Metalloproteinase Inhibitors in Age-Related Diseases

Gargiulo¹,

Gamba²,

Poli³

et al. 2014

CPD

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Degradation of the extracellular matrix is an important feature of embryonic development, morphogenesis, angiogenesis, tissue repair and remodeling. It is precisely regulated under physiological conditions, but when dysregulated it becomes a cause of many diseases, including atherosclerosis, osteoarthritis, diabetic vascular complications, and neurodegeneration. Various types of proteinases are implicated in extracellular matrix degradation, but the major enzymes are considered to be metalloproteinases such as matrix metalloproteinases (MMPs) and disintegrin and metalloproteinase domain (ADAMs) that include ADAMs with a thrombospondin domain (ADAMTS).This review discusses involvement of the major metalloproteinases in some age-related chronic diseases, and examines what is currently known about the beneficial effects of their inhibitors, used as new therapeutic strategies for treating or preventing the development and progression of these diseases.

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“…Prognostic significance of circulating MMP-3 for the existence of instable plaques is also of great interest [18] .…”

Section: Introductionmentioning

confidence: 99%

Age- and Gender-Dependent Changes in Connective Tissue Remodeling: Physiological Differences in Circulating MMP-3, MMP-10, TIMP-1 and TIMP-2 Level

et al. 2010

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Background: The mechanisms which cause age-dependent remodeling of connective tissue are still not fully understood. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) constitute an important proteolytic pathway affecting physiological matrix remodeling. Objective: The way in which changes in the extracellular matrix metabolism during the ageing process influence the level of circulating MMP-3 and MMP-10, as well as their tissue inhibitors TIMP-1 and TIMP-2, in a healthy population was investigated in this study. Methods: Blood samples were taken from 81 healthy individuals aged 6–62 years and measured for MMP-3, MMP-10, TIMP-1 and TIMP-2 levels using enzyme-linked immunosorbent assays. Polyacrylamide gel electrophoresis followed by Western immunoblotting allowed for the detection of pro- and active forms of both MMPs. Results: Serum MMP-3 and TIMP-1 values were positively correlated with age (r = 0.44, p = 0.00001 and r = 0.28, p = 0.012, respectively). A contrary tendency was found for MMP-10 and TIMP-2 serum levels. A strong age-related decrease in MMP-10 (–0.53; p = 0.000) and TIMP-2 (–0.52; p = 0.000) was noticed in our study. Gender was a significant factor modifying MMP/TIMP potential, except for the MMP-10 level. Conclusions: The data presented indicate that changes in MMP/TIMP balance occur in physiological ageing. Moreover, these findings highlight the necessity of utilizing age- and sex-matched values for analysis of MMPs and TIMPs in the pathological conditions.

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Matrix Metalloproteinases and Atherogenesis in Dependence of Age

Cited by 30 publications

References 247 publications

Macrophages: An elusive yet emerging therapeutic target of atherosclerosis

Macrophages: An elusive yet emerging therapeutic target of atherosclerosis

Metalloproteinases and Metalloproteinase Inhibitors in Age-Related Diseases

Age- and Gender-Dependent Changes in Connective Tissue Remodeling: Physiological Differences in Circulating MMP-3, MMP-10, TIMP-1 and TIMP-2 Level

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