Serum matrix metalloproteinase-9 concentration in angiographically assessed coronary artery disease

Kalela, Anne; Koivu, Tommi A.; Sisto, Tero; Kanervisto, J.; Höyhtyä, Matti; Sillanaukee, Pekka; Lehtimäki, Terho; Nikkari, Seppo T.

doi:10.1080/00365510260296483

Cited by 79 publications

(60 citation statements)

References 29 publications

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“…Our results support the recent findings suggesting that genetic variations in humans that effect MMP-9 expression influence the development and progression of atherosclerosis 8 and that elevated levels of MMP-9 in serum are seen in patients with severe coronary stenosis. 9,37 We further showed that the resident cells and not the bone marrow-derived cells were indeed the source of MMP-9 affecting the plaque composition in this model of injury-induced accelerated atherogenesis. As stated previously, we used a mixed background (50% C57BL/6 and 50% 129 SvEv) for this rapid atherogenesis.…”

Section: Discussionmentioning

confidence: 74%

Matrix Metalloproteinase-9 Modulation by Resident Arterial Cells Is Responsible for Injury-Induced Accelerated Atherosclerotic Plaque Development in Apolipoprotein E–Deficient Mice

Choi

Collins

Marine

et al. 2005

ATVB

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Objective-Although matrix metalloproteinase-9 (MMP-9) has been implicated in atherosclerotic plaque instability, the exact role it plays in the plaque development and progression remains largely unknown. We generated apolipoprotein E (apoE)-deficient (apoE Ϫ/Ϫ ) MMP-9 -deficient (MMP-9 Ϫ/Ϫ ) mice to determine the mechanisms and the main cell source of MMP-9 responsible for the plaque composition during accelerated atherosclerotic plaque formation. Methods and Results-Three weeks after temporary carotid artery ligation revealed that while on a Western-type diet, apoE Ϫ/Ϫ MMP-9 Ϫ/Ϫ mice had a significant reduction in intimal plaque length and volume compared with apoEMMP-9 ϩ/ϩ mice. The reduction in plaque volume correlated with a significantly lower number of intraplaque cells of resident cells and bone marrow-derived cells. To determine the cellular origin of MMP-9 in plaque development, bone marrow transplantation after total-body irradiation was performed with apoE Ϫ/Ϫ MMP-9 ϩ/ϩ and apoE Ϫ/Ϫ MMP-9mice, which showed that only MMP-9 derived from resident arterial cells is required for plaque development. Key Words: atherosclerosis Ⅲ MMP-9 Ⅲ bone marrow Ⅲ mouse Ⅲ compartmentalization S everal matrix metalloproteinases (MMPs), namely MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-11, and MMP-14, are present in human atherosclerotic lesions, leading to the speculation that overexpression of these enzymes is linked to atherogenesis. [1][2][3][4][5][6] However, experimental models of atherosclerosis demonstrated that mice deficient in apolipoprotein E (apoE) and MMP-3 had larger atherosclerotic plaque, whereas apoE-deficient (apoE Ϫ/Ϫ ) mice overexpressing human MMP-1 had a reduction in plaque size. 1,7 Moreover, inactivation of tissue inhibitor of metalloproteinase 1, which can inhibit MMP-1, MMP-3, MMP-9, and MMP-11 activity and is overexpressed in human atherosclerotic lesions, reduced the plaque size in apoE Ϫ/Ϫ mice. 1 Thus, it is likely that some MMPs are involved in atherogenic processes, whereas others function to inhibit plaque formation. Conclusions-MMP-9 is derived from resident arterial cells and isMMP-9 (gelatinase B) is expressed in late atherosclerotic lesions in humans and has been suggested to mediate plaque instability, a leading cause of acute coronary syndrome and stroke. 2,3 Studies in humans have revealed that polymorphisms in the MMP-9 promoter, which enhance expression, correlate with the development and progression of coronary atherosclerosis. 8,9 Studies with apoE Ϫ/Ϫ MMP-9 Ϫ/Ϫ mice have demonstrated that MMP-9 is critical to intimal plaque size. 10,11 To determine the mechanisms and the main cell source of MMP-9 responsible for the plaque composition during accelerated atherosclerotic plaque formation, we also cross-bred apoE Ϫ/Ϫ mice with MMP-9 Ϫ/Ϫ mice. We demonstrate that although MMP-9 expression is derived mostly from bone marrow cells, MMP-9 derived from resident arterial cells dictates the overall plaque composition. Therefore, MMP-9 activity associated with the resident cells (compartmental...

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Section: Discussionmentioning

confidence: 74%

Matrix Metalloproteinase-9 Modulation by Resident Arterial Cells Is Responsible for Injury-Induced Accelerated Atherosclerotic Plaque Development in Apolipoprotein E–Deficient Mice

Choi

Collins

Marine

et al. 2005

ATVB

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“…Although circulating MMP-9 levels may be elevated in patients with HF 11,22 and in patients with coronary disease, 24,25 our data suggest that plasma MMP-9 is unlikely to be an informative biomarker in a low-risk sample of the general population.…”

Section: Clinical Correlates Of Detectable Plasma Mmp-9mentioning

confidence: 72%

“…Previous investigations have been conducted in small samples of highly selected individuals. Some studies have reported that plasma MMP-9 levels are higher in patients with coronary disease, 24,25 diabetes, 26 and dyslipidemia 25 and in smokers. 27 Others have reported lower serum MMP-9 levels in hypertensive individuals.…”

mentioning

confidence: 99%

Relations of Plasma Matrix Metalloproteinase-9 to Clinical Cardiovascular Risk Factors and Echocardiographic Left Ventricular Measures

et al. 2004

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Background-Plasma levels of matrix metalloproteinase-9 (MMP-9), a key determinant of extracellular matrix degradation, are increased in heart failure and in acute coronary syndromes. We investigated cross-sectional relations of plasma MMP-9 to vascular risk factors and echocardiographic left ventricular (LV) measurements. Methods and Results-We studied 699 Framingham Study participants (mean age, 57 years; 58% women), free of heart failure and previous myocardial infarction, who underwent routine echocardiography. We examined sex-specific distributions of LV internal dimensions (LVEDD) and wall thickness (LVWT) and sampled persons with both LVEDD and LVWT below the sex-specific median (referent, nϭ299), with increased LVEDD (LVEDD Ն90th percentile, nϭ204) and increased LVWT (LVWT Ն90th percentile, nϭ221) in a 3:2:2 ratio. Plasma MMP-9 was detectable in 138 persons (20%). In multivariable models, increasing heart rate (OR per SD, 1.41; 95% CI, 1.17 to 1.71) and antihypertensive treatment (OR, 1.63; 95% CI, 1.06 to 2.50) were key clinical correlates of detectable plasma MMP-9. In multivariable-adjusted models, detectable plasma MMP-9 was associated with increased LVEDD (OR, 2.84; 95% CI, 1.13 to 7.11), increased LVWT (OR, 2.54; 95% CI, 1.00 to 6.46), and higher LV mass (Pϭ0.06) in men but not in women (OR for increased LVEDD, 1.37; 95% CI, 0.54 to 3.46; for increased LVWT, 0.99; 95% CI, 0.39 to 2.52; Pϭ0.59 for LV mass). Conclusions-In our community-based sample, detectable plasma MMP-9 levels were associated with increased LV diastolic dimensions and increased wall thickness in men. These observations indicate that plasma MMP-9 level may be a marker for cardiac extracellular matrix degradation, a process involved in LV remodeling.

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“…Regarding the role in atherosclerotic plaque, previous studies (37,38) have demonstrated that the plasma MMP-9 level in patients with coronary artery disease correlated to the severity of coronary atherosclerotic plaques and the presence of plaque rupture in the culprit lesion. The prognostic role of MMP-9 was also demonstrated by Blankenberg et al (39), who demonstrated that the MMP-9 level could be used as a predictor for cardiovascular mortality in patients with coronary artery disease (24).…”

Section: Mmps As a Prognostic Indicatormentioning

confidence: 99%

Matrix metalloproteinases and myocardial infarction

Phatharajaree

Phrommintikul

Chattipakorn

2007

Canadian Journal of Cardiology

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A cute myocardial infarction (AMI) is one of the most important health problems in many nations around the world. It may be found in many age groups, but is predominant among elderly people (1). The incidence of AMI has been increasing, possibly due to the changes in lifestyle and dietary intake that lead to an increase in coronary risk factors for cardiovascular disease.AMI has devastating consequences in the early phase, such as cardiac rupture, and in the chronic phase, such as chronic heart failure, for which the risk is mainly determined by infarct size (2). Larger infarct size induces gross morphological, histological and molecular changes of the infarcted and noninfarcted regions. These changes are known as the cardiac remodelling process. The degree of cardiac remodelling is closely related to the incidence of cardiac arrhythmias, heart failure and mortality (3). Cardiac remodelling involves changes in cardiac myocytes and in the extracellular matrix (ECM). The ECM contains a wide array of structural proteins, such as fibrillar collagen, proteoglycans and glycosaminoglycans, and serves as a reservoir for biologically active molecules. Because myocardial collagens maintain the structural integrity of adjoining myocytes and provide the means by which myocyte shortening is translated into cardiac pump function, changes in the ECM result in a loss of normal structural and functional myocardium.Matrix metalloproteinase (MMP) is a proteolytic enzyme that has been identified in the myocardium, and is likely to contribute to ECM changes and myocardial remodelling. In the past few decades, growing evidence from basic and clinical studies have demonstrated the important role of MMPs in the progression of left ventricular dimension, remodelling and mortality following AMI. In the present article, MMP expression after AMI and its role as a possible prognostic marker are reviewed. Currently available data regarding the role of MMP inhibitors as a possible novel therapeutic intervention are also discussed. Acute myocardial infarction (AMI) is currently one of the most important health problems in many countries around the world. Following AMI, many cytokines and proteolytic enzymes are released. Among these, matrix metalloproteinases (MMPs) are important proteolytic enzymes that lead to degradation of the extracellular matrix and to changes in cardiomyocytes in both infarcted and noninfarcted myocardium. This process is known as cardiac remodelling. It has been demonstrated that more than one type of MMP is present in the circulation after cardiomyocyte injury. A number of studies have demonstrated the correlations between these MMP levels and the severity of a coronary lesion, the progression of left ventricular dimension and the survival rate following AMI in both animal and human studies. MMPs have also been proposed as a possible novel prognostic indicator for myocardial infarction patients. Although the use of MMP inhibitors to improve cardiac outcome in AMI patients has been investigated, discrepancies in the re...

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Serum matrix metalloproteinase-9 concentration in angiographically assessed coronary artery disease

Cited by 79 publications

References 29 publications

Matrix Metalloproteinase-9 Modulation by Resident Arterial Cells Is Responsible for Injury-Induced Accelerated Atherosclerotic Plaque Development in Apolipoprotein E–Deficient Mice

Matrix Metalloproteinase-9 Modulation by Resident Arterial Cells Is Responsible for Injury-Induced Accelerated Atherosclerotic Plaque Development in Apolipoprotein E–Deficient Mice

Relations of Plasma Matrix Metalloproteinase-9 to Clinical Cardiovascular Risk Factors and Echocardiographic Left Ventricular Measures

Matrix metalloproteinases and myocardial infarction

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