Myocardial proteases and matrix remodeling in inflammatory heart disease

Rutschow, Susanne; Li, Jun; Schultheiss, Heinz‐Peter; Pauschinger, Matthias

doi:10.1016/j.cardiores.2005.12.009

Cited by 99 publications

(75 citation statements)

References 109 publications

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“…Alteration in the matrix degradation system caused by inflammatory mediators, oxygen species, and neurohumoral reactions leads to an impairment of LV function as observed in myocarditis and inflammatory cardiomyopathy. 23 The imbalance of the matrix-degrading system with induced expressions of MMPs and plasminogen activators as well as the reduced expressions of tissue inhibitors of MMPs leads to a pathologic collagen turnover, with the loss of structural integrity of the heart and an impairment of LV function. 23 Interestingly, we could observe an increase in myocardial mRNA levels of MMP-2 and -9 in rats with DCM ( Figure 5).…”

Section: Discussionmentioning

confidence: 99%

“…23 The imbalance of the matrix-degrading system with induced expressions of MMPs and plasminogen activators as well as the reduced expressions of tissue inhibitors of MMPs leads to a pathologic collagen turnover, with the loss of structural integrity of the heart and an impairment of LV function. 23 Interestingly, we could observe an increase in myocardial mRNA levels of MMP-2 and -9 in rats with DCM ( Figure 5). It is reported that AT 1 R may be involved in the development of cardiac hypertrophy by increasing ECM ±dP/dt, rate of intra-ventricular pressure rise and decline; EAM, experimental autoimmune myocarditis; EF, ejection fraction; FS, fractional shortening; group N, aged-matched untreated rats; group T10, rats with heart failure treated with telmisartan (10 mg kg -1 day -1 ); group V, rats with heart failure treated with vehicle; HR, heart rate; HW, heart weight; HW/BW, ratio of heart weight to body weight; LVDd, left ventricular dimension in diastole; LVDs, left ventricular dimension in systole; LVEDP, left ventricular end-diastolic pressure; LVP, left ventricular pressure; MBP, mean blood pressure; n, no.…”

Section: Discussionmentioning

confidence: 99%

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Telmisartan, an angiotensin-II receptor blocker ameliorates cardiac remodeling in rats with dilated cardiomyopathy

et al. 2010

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Multiple trials over the past several years have examined indications for angiotensin receptor blockers (ARBs) in the treatment of left ventricular (LV) dysfunction, both acutely after myocardial infarction and in chronic heart failure (CHF). However, the effects of telmisartan, an ARB in rats with CHF after experimental autoimmune myocarditis (EAM) have not yet been analyzed. CHF was elicited in Lewis rats by immunization with cardiac myosin, and 28 days after immunization, the surviving Lewis rats were divided into two groups and treated with either telmisartan (10 mg kg -1 day -1 ) or vehicle. After 4 weeks of treatment, we analyzed the effects of telmisartan on cardiac function, proinflammatory cytokines and cardiac remodeling in EAM rats. Myocardial functional parameters measured by hemodynamic and echocardiographic studies were significantly improved by telmisartan treatment in rats with CHF compared with those of vehicle-treated rats with CHF. Telmisartan significantly reduced levels of cardiac fibrosis, hypertrophy and its marker molecules (LV mRNA expressions of transforming growth factor beta 1, collagen I and III, and atrial natriuretic peptide), and peroxisome proliferator-activated receptor-c protein expression compared with those of vehicle-treated rats. CHF-induced increases in myocardial mRNA expressions of proinflammatory cytokines, (interleukin (IL)-6, IL-1b), monocyte chemoattractant protein-1 and matrix metalloproteinases (MMP-2 and -9) were also suppressed by the treatment with telmisartan. Moreover, the plasma level of angiotensin-II was significantly elevated in telmisartan-treated rats. Our results indicate that telmisartan treatment significantly improved LV function and ameliorated the progression of cardiac remodeling in rats with CHF after EAM.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Telmisartan, an angiotensin-II receptor blocker ameliorates cardiac remodeling in rats with dilated cardiomyopathy

et al. 2010

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“…Thus a heterogeneous pattern of ECM remodeling occurs in ischemic DCM where enhanced ECM accumulation and degradation occur simultaneously. In cases of infectious DCM, the robust inflammatory response within the myocardium heralds the induction of cytokine and growth factor receptor pathways which can augment ECM synthesis and accumulation (71,221,228,325,372). Using a selective corrosive technique which reveals the collagen skeletal framework amenable for scanning electron microscopy, Rossi (368) demonstrated that significant ECM remodeling occurred in patients with DCM secondary to Chagastic myocarditis (221).…”

Section: Myocardial Remodeling In Cardiomyopathic Diseasementioning

confidence: 99%

Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function

Spinale¹

2007

Physiological Reviews

1,005

1,023

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It is now becoming apparent that dynamic changes occur within the interstitium that directly contribute to adverse myocardial remodeling following myocardial infarction (MI), with hypertensive heart disease and with intrinsic myocardial disease such as cardiomyopathy. Furthermore, a family of matrix proteases, the matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs), has been recognized to play an important role in matrix remodeling in these cardiac disease states. The purpose of this review is fivefold: 1) to examine and redefine the myocardial matrix as a critical and dynamic entity with respect to the remodeling process encountered with MI, hypertension, or cardiomyopathic disease; 2) present the remarkable progress that has been made with respect to MMP/TIMP biology and how it relates to myocardial matrix remodeling; 3) to evaluate critical translational/clinical studies that have provided a cause-effect relationship between alterations in MMP/TIMP regulation and myocardial matrix remodeling; 4) to provide a critical review and analysis of current diagnostic, prognostic, and pharmacological approaches that utilized our basic understanding of MMP/TIMPs in the context of cardiac disease; and 5) most importantly, to dispel the historical belief that the myocardial matrix is a passive structure and supplant this belief that the regulation of matrix protease pathways such as the MMPs and TIMPs will likely yield a new avenue of diagnostic and therapeutic strategies for myocardial remodeling and the progression to heart failure.

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“…26,37 Altered MMP expression and activation can lead to an imbalance between collagen synthesis/degradation in the myocardial ECM 37,38 and a change in the structural integrity of the heart. 26,39 In the adult heart, the role of MMPs is associated with repair and protection in response to pathological injury 39 ; while in the immature heart, MMPs play an essential role in tissue remodeling and cell migration. 27 Growth of the fetal heart occurs by both hyperplasia and hypertrophy of cardiomyocytes 40 and structural integrity of the myocardium is regulated by the complex balance of synthesis/degradation of ECM components such as fibrillar collagens.…”

Section: Role Of Mmps In Cardiac Remodelingmentioning

confidence: 99%

“…25,26 Both the inflammatory response and oxidative stress have been shown to favor the activation of MMPs as well as regulating gene transcription in heart tissue. 26,27 Metalloproteinases are important enzymes that contribute to cardiac remodeling.…”

Section: Introductionmentioning

confidence: 99%

Prenatal Nicotine Increases Matrix Metalloproteinase 2 (MMP-2) Expression in Fetal Guinea Pig Hearts

et al. 2011

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This study tested the hypothesis that maternal nicotine ingestion increases matrix metalloproteinase (MMP) expression in fetal hearts, which is mediated by the generation of reactive oxygen species. Timed pregnant guinea pigs were administered either water alone, nicotine (200 mg/mL), N-acetylcysteine (NAC), or nicotine plus NAC in their drinking water for 10 days at 52-day gestation (term ¼ 65 days). Near-term (62 days), anesthetized fetuses were extracted, hearts were excised, and left cardiac ventricles snap frozen for analysis of MMP-2/-9/-13 protein and activity levels. Interstitial collagens were identified by Picrosirius red stain to assess changes in the extracellular matrix. Prenatal nicotine increased active MMP-2 forms and interstitial collagen but had no effect on either pro-or active MMP-9 or MMP-13 forms. In the presence of nicotine, NAC decreased active MMP-2 protein levels and reversed the nicotine-induced increase in collagen staining. We conclude that prenatal nicotine alters MMP-2 expression in fetal hearts that may be mediated by reactive oxygen species generation.

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Myocardial proteases and matrix remodeling in inflammatory heart disease

Cited by 99 publications

References 109 publications

Telmisartan, an angiotensin-II receptor blocker ameliorates cardiac remodeling in rats with dilated cardiomyopathy

Telmisartan, an angiotensin-II receptor blocker ameliorates cardiac remodeling in rats with dilated cardiomyopathy

Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function

Prenatal Nicotine Increases Matrix Metalloproteinase 2 (MMP-2) Expression in Fetal Guinea Pig Hearts

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