Delayed Reperfusion Alters Matrix Metalloproteinase Activity and Fibronectin mRNA Expression in the Infarct Zone of the Ligated Rat Heart

Carlyle, Wenda C.; Jacobson, Andrew; Judd, Dianne; Tian, Bin; Chu, Cuixia; Hauer, K; Hartman, Malinda; McDonald, Kenneth

doi:10.1006/jmcc.1997.0482

Cited by 55 publications

(31 citation statements)

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“…Consistent with previous studies (2,6,23), the LV MMP-2 level was persistently activated after MI (Fig. 3).…”

Section: Discussionsupporting

confidence: 92%

“…Among the various known MMPs, MMP-9 has been shown to play an important role in post-MI remodeling (7), and it is mainly expressed in such infiltrating inflammatory cells as neutrophils and macrophages (14,25). Conversely, MMP-2 is ubiquitously distributed in cardiac myocytes and fibroblasts (3), and it has been shown to be persistently upregulated after MI (2,6,23). Therefore, MMP-2 may play an important role in early myocardial healing and the late postinfarct remodeling process.…”

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confidence: 99%

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Targeted deletion of MMP-2 attenuates early LV rupture and late remodeling after experimental myocardial infarction

Hayashidani¹,

Tsutsui²,

Ikeuchi³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

284

233

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. Targeted deletion of MMP-2 attenuates early LV rupture and late remodeling after experimental myocardial infarction. Am J Physiol Heart Circ Physiol 285: H1229-H1235, 2003. First published May 29, 2003 10.1152/ ajpheart.00207.2003.-Matrix metalloproteinase-2 (MMP-2) is prominently overexpressed both after myocardial infarction (MI) and in heart failure. However, its pathophysiological significance in these conditions is still unclear. We thus examined the effects of targeted deletion of MMP-2 on post-MI left ventricular (LV) remodeling and failure. Anterior MI was produced in 10-to 12-wk-old male MMP-2 knockout (KO) and sibling wild-type (WT) mice by ligating the left coronary artery. By day 28, MI resulted in a significant increase in mortality in association with LV cavity dilatation and dysfunction. The MMP-2 KO mice had a significantly better survival rate than WT mice (56% vs. 85%, P Ͻ 0.05), despite a comparable infarct size (50 Ϯ 3% vs. 51 Ϯ 3%, P ϭ not significant), heart rate, and arterial blood pressure. The KO mice had a significantly lower incidence of LV rupture (10% vs. 39%, P Ͻ 0.05), which occurred within 7 days of MI. The KO mice exerted less LV cavity dilatation and improved fractional shortening after MI by echocardiography. The LV zymographic MMP-2 level significantly increased in WT mice after coronary artery ligation; however, this was completely prevented in KO mice. In contrast, the increase in the LV zymographic MMP-9 level after MI was similar between KO and WT mice. MMP-2 activation is therefore considered to contribute to an early cardiac rupture as well as late LV remodeling after MI. The inhibition of MMP-2 activation may therefore be a potentially useful therapeutic strategy to manage post-MI hearts. matrix metalloproteinase; cardiac rupture; heart failure; myocyte; extracellular matrix; mouse MYOCARDIAL INFARCTION (MI) leads to complex structural alterations (remodeling) involving both the infarcted and noninfarcted left ventricular (LV) myocardium (21). Early remodeling as LV cavity dilatation occurs during the early phase of MI, which is likely due to wall thinning in the infarct region. This might lead to a cardiac rupture, thereby accounting for the 5-30% of in-hospital mortality after acute MI (1). During the first several days, LV enlargement follows, and, thereafter, a progressive dilatation of the noninfarcted LV occurs over weeks (21). These progressive changes in LV geometry contribute to the development of depressed cardiac function, clinical heart failure, and increased mortality. Accordingly, it is of critical importance to explore the mechanisms of LV remodeling and develop therapeutic strategies that will effectively inhibit this deleterious process.The dynamic synthesis and breakdown of extracellular matrix (ECM) proteins play an important role in post-MI LV remodeling. In particular, the increased expression and activation of matrix metalloproteinases (MMPs) have been implicated in this process (4,5). Several studies have demonstrated that MMPs are involved not...

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“…Consistent with previous studies (2,6,23), the LV MMP-2 level was persistently activated after MI (Fig. 3).…”

Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Targeted deletion of MMP-2 attenuates early LV rupture and late remodeling after experimental myocardial infarction

Hayashidani¹,

Tsutsui²,

Ikeuchi³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

284

233

View full text Add to dashboard Cite

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“…It is now known that myocardial MMPs are produced by fibroblast-like cells, inflammatory cells, as well as by cardiomyocytes [34,35], that they are predominantly present in their latent form [36], and that they are increasingly expressed and activated in several pathological conditions of the heart. A number of studies have demonstrated increased expression and activity of MMP-1, -2, -3, and -9 in human, rat, and porcine hearts during the remodelling process after MI [35][36][37][38][39][40]. Although the data on the exact time course of postinfarction myocardial MMP activity is diverse, it becomes increasingly clear that MMP activation starts early (<1 day after MI) [40].…”

Section: S Heeneman Et Almentioning

confidence: 99%

The dynamic extracellular matrix: intervention strategies during heart failure and atherosclerosis

Heeneman

Cleutjens

Faber

et al. 2003

The Journal of Pathology

120

106

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The extracellular matrix is no longer seen as the static embedding in which cells reside; it has been shown to be involved in cell proliferation, migration and cell-cell interactions. Turnover of the different extracellular matrix components is an active process with multiple levels of regulation. Collagen, a major extracellular matrix constituent of the myocardium and the arterial vascular wall, is synthesized by (myo)fibroblasts in the myocardium and smooth muscle cells in the medial arterial vascular wall. Its degradation is controlled by proteinases, which include matrix metalloproteinases. This review will focus on the impact of fibrosis and especially collagen turnover on the progression of heart failure and atherosclerosis, two of the main cardiovascular pathologies. We will discuss data from human studies and animal models, with an emphasis on the effects of interventions on collagen synthesis and degradation. We conclude that there is a dynamic (dis)balance in the rate of collagen synthesis and degradation during heart failure and atherosclerosis, which makes the outcome of interventions not always predictable. Alternative approaches for intervening in collagen metabolism will be discussed as possible therapeutic intervention strategies.

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“…20,21 Early after MI, the infarcted region of the LV undergoes myocyte necrosis, apoptosis, 18,22 and ECM reorganization. [23][24][25][26][27] Late remodeling in the remote LV may also involve changes in ECM. 28 Alterations in ECM, in particular, increased collagen accumulation 29,30 and changes in the activity of MMPs and tissue inhibitors of metalloproteinase, 2 have been observed in the remote myocardium after MI.…”

mentioning

confidence: 99%

Exaggerated Left Ventricular Dilation and Reduced Collagen Deposition After Myocardial Infarction in Mice Lacking Osteopontin

Trueblood

Xie

Communal

et al. 2001

Circulation Research

274

264

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Abstract-Osteopontin (OPN), an extracellular matrix protein, is expressed in the myocardium with hypertrophy and failure. We tested the hypothesis that OPN plays a role in left ventricular (LV) remodeling after myocardial infarction (MI). Accordingly, OPN expression and LV structural and functional remodeling were determined in wild-type (WT) and OPN knockout (KO) mice 4 weeks after MI. Northern analysis showed increased OPN expression in the infarcted region, peaking 3 days after MI and gradually decreasing over the next 28 days. In the remote LV, OPN expression was biphasic, with peaks at 3 and 28 days. In situ hybridization and immunohistochemical analyses showed increased OPN mRNA and protein primarily in the interstitium. Infarct size, heart weight, and survival were similar in KO and WT mice after MI (PϭNS), whereas the lung wet weight/dry weight ratio was increased in the KO mice (PϽ0.005 versus sham-operated mice). Peak LV developed pressure was reduced to a similar degree after MI in the KO and WT mice. Key Words: extracellular matrix proteins Ⅲ osteopontin Ⅲ collagen Ⅲ myocyte slippage Ⅲ myocyte elongation T he dynamic synthesis and breakdown of extracellular matrix (ECM) proteins may play an important role in myocardial remodeling. 1,2 Recently, using spontaneously hypertensive and aortic-banded rats, we showed increased expression of osteopontin (OPN), an ECM protein, coincident with the development of heart failure. 3 Although first isolated from mineralized bone matrix, OPN has since been shown to be synthesized by several cell types, including cardiac myocytes, microvascular endothelial cells, and fibroblasts. 4 -6 OPN, an adhesive glycophosphoprotein with an arginineglycine-aspartic acid (RGD) sequence, has been shown to interact with integrins (␣ V ␤ 3 , ␣ V ␤ 1 , and ␣ V ␤ 5 ) and the CD44 receptor in an RGD-dependent manner. 4,7 OPN appears capable of mediating diverse biological functions, including cell adhesion, chemotaxis, and signaling. 4,8 OPN has also been shown to interact with fibronectin and collagen, suggesting its possible role in matrix organization and/or stability. 9 -11 Recently, using a mammary cell line, we observed that suppression of OPN synthesis leads to increased activity of matrix metalloproteinase (MMP)-2. 12 In fact, there is increased expression of OPN in several tissues in response to injury, suggesting a role in wound healing. Using a skin incision model, Liaw et al 13 observed disorganization of the matrix and alteration of collagen fibrillogenesis, leading to collagen fibrils with smaller diameters in OPN knockout (KO) mice. Similarly, OPN has been shown to play a critical role in the generation of interstitial fibrosis in the kidney after obstructive nephropathy. 14 Remodeling after myocardial infarction (MI) is associated with left ventricular (LV) dilation, decreased cardiac function, and increased mortality. 15 Early dilation of the LV is likely due to scar expansion in the infarcted region, 16 -18 followed later by progressive remodeling 19 in the noninf...

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Delayed Reperfusion Alters Matrix Metalloproteinase Activity and Fibronectin mRNA Expression in the Infarct Zone of the Ligated Rat Heart

Cited by 55 publications

References 0 publications

Targeted deletion of MMP-2 attenuates early LV rupture and late remodeling after experimental myocardial infarction

Targeted deletion of MMP-2 attenuates early LV rupture and late remodeling after experimental myocardial infarction

The dynamic extracellular matrix: intervention strategies during heart failure and atherosclerosis

Exaggerated Left Ventricular Dilation and Reduced Collagen Deposition After Myocardial Infarction in Mice Lacking Osteopontin

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