Do metalloproteinases destabilize vulnerable atherosclerotic plaques?

Current Opinion in Lipidology

Volumn 17, Issue 5, 2006, Pages 556-561

  Newby, Andrew C ^a,b  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

^b BRISTOL ROYAL INFIRMARY   (United Kingdom)

Author keywords

Atherosclerosis; Extracellular matrix; Metalloproteinases; Myocardial infarction; Plaque rupture

Indexed keywords

APOLIPOPROTEIN A1; GLUCOSE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; INSULIN; RIMONABANT; SIBUTRAMINE; TETRAHYDROLIPSTATIN; TRIACYLGLYCEROL;

ATHEROSCLEROSIS; BEHAVIOR MODIFICATION; CARDIOVASCULAR EFFECT; FITNESS; GLUCOSE TOLERANCE; HUMAN; HYPERHOMOCYSTEINEMIA; INBORN ERROR OF METABOLISM; INSULIN SENSITIVITY; LIFESTYLE; LIPID BLOOD LEVEL; MEDITERRANEAN DIET; METABOLIC REGULATION; NUTRITIONAL STATUS; OBESITY; PHYSICAL ACTIVITY; PRIORITY JOURNAL; REVIEW; RISK FACTOR; SITTING; SMOKING; THROMBOSIS; WEIGHT REDUCTION;

ANIMALS; ATHEROSCLEROSIS; HUMANS; MATRIX METALLOPROTEINASES; MICE; MICE, KNOCKOUT; MODELS, BIOLOGICAL; PROTEASE INHIBITORS;

ORYCTOLAGUS CUNICULUS;

EID: 33748550024     PISSN: 09579672     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.mol.0000245262.48258.b4     Document Type: Review

References (37)

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37. Pearce E, Tregouet D-A, Samnegard A, et al. Haplotype effect of the matrix metalloproteinase-1 gene on risk of myocardial infarction. Circ Res 2005; 97:1070-1076. The authors identified seven promoter polymorphisms, i.e. -1607 (GG/G, i.e. G insertion/deletion), -839 (G/A), -755 (G/T), -519 (A/G), -422 (T/A), -340 (T/C), and -320 (T/C), and two silent mutations in the coding region of the MMP 1 gene. Although no individual promoter polymorphism predicted myocardial infarction, both the A-519-C-340 and G-519-T-340 haplotypes had 30% less chance of myocardial infarction, whereas the G-519-C-340 haplotype had almost 100% more chance of myocardial infarction compared with the A-519-T-340 haplotype. Exceptionally, the results were replicated in a Swedish population. The haplotypes associated with protection from myocardial infarction caused lower promoter activity in THP-1 monocytic cells in vitro and reduced binding of promoter fragments to THP-1 DNA and, where measurable, gave lower levels of MMP 1 mRNA in carotid endarterectomy tissues. The study provides additional strong support for an association between increased MMP 1 activity and myocardial infarction in humans.