Deficiency of TIMP-1 exacerbates LV remodeling after  myocardial infarction in mice

Creemers, Esther E.; Davis, Jeniffer N.; Parkhurst, Andrea M.; Leenders, Peter; Dowdy, Kathryn B.; Hapke, Elizabeth; Hauet, Anne; Escobar, Patricia G.; Cleutjens, Jack P.M.; Smits, J. F. M.; Daemen, M. J. A. P.; Zile, Michael R.; Spinale, Francis G.

doi:10.1152/ajpheart.00511.2002

Cited by 173 publications

(141 citation statements)

References 34 publications

(55 reference statements)

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“…MMP-2 knockout mice also had greater survival after AMI and less left ventricular adverse remodelling (18,46). Selective inhibition of TIMP-1 in TIMP-1 knockout mice has also been shown to exacerbate left ventricular remodelling after AMI (48). The role of TIMP-1 activity alteration was confirmed by Jayasankar et al (49), who demonstrated that in left coronary artery ligation-induced MI in rats, TIMP-1 gene transfer inhibited MMP activity, and preserved cardiac function and geometry in ischemic cardiomyopathy.…”

Section: Mmp Inhibitors and Ami In Animal Modelsmentioning

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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Section: Mmp Inhibitors and Ami In Animal Modelsmentioning

confidence: 99%

Matrix metalloproteinases and myocardial infarction

Phatharajaree

Phrommintikul

Chattipakorn

2007

Canadian Journal of Cardiology

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“…1,22 Transgenic TIMP-1 Ϫ/Ϫ mice have increased end-diastolic LV volumes, increased end-diastolic LV pressures, and decreased contractility after MI. 23 In addition, chronic myocardial MMP-1 overexpression leads to marked systolic and diastolic cardiac dysfunction in animal models. 24 Transgenic MMP-9 Ϫ/Ϫ mice have reduced LV remodeling and rupture after MI, 25 suggesting that enhanced post-MI MMP activity is an important contributor to subsequent morbidity and mortality.…”

Section: Jayasankar Et Al Timp-1 Gene Transfer Treats Ischemic Cardiomentioning

confidence: 99%

Inhibition of Matrix Metalloproteinase Activity by TIMP-1 Gene Transfer Effectively Treats Ischemic Cardiomyopathy

et al. 2004

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Background-Enhanced activity of matrix metalloproteinases (MMPs) has been associated with extracellular matrix degradation and ischemic heart failure in animal models and human patients. This study evaluated the effects of MMP inhibition by gene transfer of TIMP-1 in a rat model of ischemic cardiomyopathy. Methods and Results-Rats underwent ligation of the left anterior descending coronary artery with direct intramyocardial injection of replication-deficient adenovirus encoding TIMP-1 (nϭ8) or null virus as control vector (nϭ8), and animals were analyzed after 6 weeks. Both systolic and diastolic cardiac function was significantly preserved in the TIMP-1 group compared with control animals (maximum left ventricular [LV] pressure: TIMP-1 70Ϯ10 versus control 56Ϯ12 mmHg, PϽ0.05; maximum dP/dt 2697Ϯ842 versus 1622Ϯ527 mmHg/sec, PϽ0.01; minimum dP/dt

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“…The second system involved in ECM remodeling in the heart is the matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) system [14]. In the failing heart, down-regulation of TIMPs alters the ECM equilibrium toward matrix degradation and leads to an increase in tissue turnover and accelerated remodeling [15].…”

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confidence: 99%