Matrix metalloproteinase-1 and tissue inhibitors do not predict incident coronary artery disease in the atherosclerosis risk in communities (ARIC) study.

Section of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital (Impact Factor: 0.65). 02/2008; 35(4):388-94.
Source: PubMed


Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) are thought to be associated with coronary artery disease. The association of these markers with incident coronary artery disease has not been well described. Using a case-cohort design, we selected 216 individuals who had incident coronary artery disease (case group) and 225 individuals from a cohort random sample (comparison group) from participants enrolled in the Atherosclerosis Risk in Communities study. We measured plasma levels of MMP-1 and TIMP-1, traditional risk factors, and other markers of inflammation. We found no significant difference in TIMP-1 levels between the case group (827.8 +/- 23.8 ng/mL) and the comparison group (819.31 +/- 16.1 ng/mL) (P=0.77), and no significant difference in the frequency of MMP-1 levels that were dichotomized at the minimum detectable value of 1.7 ng/mL (P=0.49). In models adjusted for age, sex, race, body mass index, hypertension, diabetes, total cholesterol, high-density lipoprotein cholesterol, triglycerides, fibrinogen, von Willebrand factor, and white blood cell count, the hazard-rate ratio for incident coronary artery disease was 1.14 (95% confidence interval, 0.63-2.04; P=0.67) for individuals whose TIMP-1 levels were above, versus at or below the mean, and 1.17 (95% confidence interval, 0.63-2.19; P=0.62) for individuals whose MMP-1 levels were above 1.7 ng/mL. We conclude that TIMP-1 and MMP-1 levels in plasma were not predictive of incident coronary artery disease in a case-cohort random sample of the Atherosclerosis Risk in Communities study, a population study of asymptomatic middle-aged adults who had no prevalent atherosclerosis upon enrollment.

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Available from: Charles Etta Rhodes, Jan 09, 2015
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    • "This is the first report of the prospective relationship between markers of ECM remodelling and risk of incident AF. Previous studies have published on the relationship between markers of ECM remodelling with CHD [5], [6], [29], but the results have been inconsistent with studies reporting either a positive or null effect while others have shown that markers of inflammation largely confound the association. In a publication from the ARIC group, plasma levels of TIMP-1 and MMP-1 were unrelated to increased risk of coronary artery disease [5] whereas in Framingham, plasma TIMP-1 levels were positively associated with cardiovascular incidence and death [29]. "
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    ABSTRACT: Previous cross-sectional studies have suggested that biomarkers of extracellular matrix remodelling are associated with atrial fibrillation (AF), but no prospective data have yet been published. Hence, we examine whether plasma matrix metalloproteinases (MMP) and their inhibitors are related to increased risk of incident AF. We used a case-cohort design in the context of the prospective Atherosclerosis Risk in Communities (ARIC) study. From 13718 eligible men and women free from AF in 1990-92, we selected a stratified random sample of 500 individuals without and 580 with incident AF over a mean follow-up of 11.8 years. Using a weighted proportional hazards regression model, the relationships between MMP-1, MMP-2, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1, TIMP-2 and C-terminal propeptide of collagen type-I with incident AF were examined after adjusting for confounders. In models adjusted for age, sex and race, all biomarkers were associated with AF, but only the relationship between plasma MMP-9 remained significant in the fully-adjusted model: each one standard deviation increase in MMP-9 was associated with 27% (95% Confidence Interval: 7% to 50%) increase in risk of AF with no evidence of an interaction with race or sex. Individuals with above mean levels of MMP-9 were more likely to be male, white and current smokers. The findings suggest that elevated levels of MMP-9 are independently associated with increased risk of AF. However, given the lack of specificity of MMP-9 to atrial tissue, it remains to be determined whether the observed relationship reflects the impact of atrial fibrosis or more generalized fibrosis on risk of incident AF.
    PLoS ONE 03/2013; 8(3):e59052. DOI:10.1371/journal.pone.0059052 · 3.23 Impact Factor
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    • "This is in contradiction with the results of the present study. Nambi et al. investigated the levels of MMP-1 in patients with coronary artery disease [17]. They have not found any difference and concluded that MMP-1 can not be used as a prognostic biomarker for coronary artery disease. "
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    ABSTRACT: Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent proteases (endopeptidases) whose catalytic action is the degradation of the extracellular matrix components. In addition, they play the major role in the degradation of collagen and in the process of tissue remodeling. The present clinical study investigated blood serum levels of metalloproteinases- 1, -2, -3 and -9 in patients with acute and chronic aortic dissection, thoracic aortic aneurysm and acute myocardial ischemia compared to healthy individuals. The blood serum levels of MMP-1, -2, -3 and -9 were calculated in 31 patients with acute aortic dissection, 18 patients with chronic aortic dissection, 18 patients with aortic aneurysm and in 13 patients with acute myocardial ischemia, as well as in 15 healthy individuals who served as the control group. Serum MMP levels were measured by using an ELISA technique. There were significantly higher levels of MMP-3 in patients with acute myocardial ischemia as compared to acute aortic dissection (17.33 +/- 2.03 ng/ml versus 12.92 +/- 1.01 ng/ml, p < 0.05). Significantly lower levels of MMP-1 were found in healthy controls compared to all groups of patients (1.1 +/- 0.38 ng/ml versus 2.97 +/- 0.68 in acute aortic dissection, 3.09 +/- 0.98 in chronic dissection, 3.16 +/- 0.51 in thoracic aortic aneurysm and 4.58 +/- 1.04 in acute myocardial ischemia, p < 0.05). Higher levels of MMP-1 and MMP-3 were detected on males. There was a positive correlation with increasing age (r = 0.38, p < 0.05). In patients operated for acute type A aortic dissection, the levels of MMP-1, MMP-3 and MMP-9 increased immediately after surgery, while the levels of MMP-2 decrease. At 24 hours postoperatively, levels of MMP -1, -2 and -9 are almost equal to the preoperative ones. Measurement of serum MMP levels in thoracic aortic disease and acute myocardial ischemia is a simple and relatively rapid laboratory test that could be used as a biochemical indicator of aortic disease or acute myocardial ischemia, when evaluated in combination with imaging techniques.
    Journal of Cardiothoracic Surgery 11/2009; 4(1):59. DOI:10.1186/1749-8090-4-59 · 1.03 Impact Factor
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    ABSTRACT: To examine the relationship of plasma levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase 1 (TIMP-1) with carotid artery characteristics measured by MRI in a cross-sectional investigation among Atherosclerosis Risk in Communities Carotid MRI Study participants. A stratified random sample was recruited based on intima-media thickness from a previous ultrasonographic examination. A high-resolution gadolinium-enhanced MRI examination of the carotid artery was performed from 2004 to 2005 on 1901 Atherosclerosis Risk in Communities cohort participants. Multiple carotid wall characteristics, including wall thickness, lumen area, calcium area, lipid core, and fibrous cap measures, were evaluated for associations with plasma MMPs 1, 2, 3, 7, 8, and 9 and TIMP-1. Plasma MMPs 1, 3, and 7 were significantly higher among participants in the high intima-media thickness group compared with those in the low intima-media thickness group. The normalized wall index was independently associated with MMPs 3 and 7 and TIMP-1. MMP-7 was positively associated with carotid calcification. The mean fibrous cap thickness was significantly higher in individuals with elevated TIMP-1 levels. In addition, TIMP-1 was positively associated with measures of lipid core. Circulating levels of specific MMPs and TIMP-1 were associated with carotid wall remodeling and structural changes related to plaque burden in elderly participants.
    Arteriosclerosis Thrombosis and Vascular Biology 02/2010; 30(5):1034-42. DOI:10.1161/ATVBAHA.109.195370 · 6.00 Impact Factor