Metalloproteinases-2 and -9 Predict Left Ventricular Remodeling after Myocardial Infarction

Cogni, Ana Lúcia; Farah, E; Minicucci, Marcos F.; Azevedo, Paula Schmidt; Okoshi, Katashi; Matsubara, Beatriz Bojikian; Zanati, Silméia Garcia; Haggeman, Rodrigo; Paiva, Sérgio Alberto Rupp de; Zornoff, Leonardo A. M.

doi:10.5935/abc.20130049

Cited by 22 publications

(22 citation statements)

References 36 publications

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“…Underscoring the disease relevance of MMP-2-mediated cardiac injury, studies in humans have implicated MMP-2 in LV dysfunction and dysfunctional remodeling after myocardial infarction (Nilsson et al, 2011; Cogni et al, 2013). Previous studies report decreased in-vivo function due to transgenic expression of FL-MMP-2 (Bergman et al, 2007) or NTT-MMP-2 (Lovett et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…The most serious complication of post-infarction remodeling is congestive heart failure, which has become one of the leading causes of death in ischemic cardiac disease. Recent experimental and clinical evidence has underscored a critical role for matrix metalloproteinase-2 (MMP-2) in ischemic cardiac disease, including post-infarction ventricular remodeling (Alfonso-Jaume et al, 2006; Mukherjee et al, 2006; Bergman et al, 2007; Zhou et al, 2007; Nilsson et al, 2011; Lovett et al, 2012, 2013; Cogni et al, 2013). Our current gaps in knowledge are substantial and relate to an incomplete understanding of the multiple pathophysiologic roles of MMP-2 in post-infarction remodeling.…”

Section: Introductionmentioning

confidence: 99%

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A N-terminal truncated intracellular isoform of matrix metalloproteinase-2 impairs contractility of mouse myocardium

et al. 2014

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The full-length isoform of matrixmetalloproteinase-2 (FL-MMP-2) plays a role in turnover of the cardiac extracellular matrix. FL-MMP-2 is also present intracellularly in association with sarcomeres and, in the setting of oxidative stress, cleaves myofilament proteins with resultant impaired contractility. Recently, a novel N-terminal truncated MMP-2 isoform (NTT-MMP-2) generated during oxidative stress was identified and shown to induce severe systolic failure; however, the injury mechanisms remained unclear. In this study, cardiac-specific NTT-MMP-2 transgenic mice were used to determine the physiological effects of NTT-MMP-2 on: force development of intact myocardium; the function of cardiac myofilaments in demembranated myocardium; and on intracellular Ca2+ transients in isolated myocytes. We related the contractile defects arising from NTT-MMP-2 expression to the known intracellular locations of NTT-MMP-2 determined using immunohistochemistry. Comparison was made with the pathophysiology arising from cardiac-specific FL-MMP-2 transgenic mice. Consistent with previous studies, FL-MMP-2 was localized to myofilaments, while NTT-MMP-2 was concentrated within subsarcolemmal mitochondria and to sites in register with the Z-line. NTT-MMP-2 expression caused a 50% reduction of force development by intact myocardium. However, NTT-MMP-2 expression did not reduce myofilament force development, consistent with the lack of NTT-MMP-2 localization to myofilaments. NTT-MMP-2 expression caused a 50% reduction in the amplitude of Ca2+ transients, indicating impaired activation.Conclusions: Unlike FL-MMP-2, NTT-MMP-2 does not mediate myofilament damage. Instead, NTT-MMP-2 causes impaired myocyte activation, which may involve effects due to localization in mitochondria and/or to transverse tubules affecting Ca2+ transients. Thus, FL-MMP-2 and NTT-MMP-2 have discrete intracellular locations and mediate different intracellular damage to cardiac myocytes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A N-terminal truncated intracellular isoform of matrix metalloproteinase-2 impairs contractility of mouse myocardium

et al. 2014

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“…The balance between TIMP and MMP exerts an important role in myocardial fibrosis. MMP2 and MMP9 have been proven to play vital roles in cardiac remodeling [27]. Previously basic studies revealed that treatment with CCM decreased MMP-1, MMP-2 and MMP-9 mRNA and protein expression, without affecting TIMP expression [15].…”

Section: Discussionmentioning

confidence: 99%

Cardiac Contractility Modulation Attenuate Myocardial Fibrosis by Inhibiting TGF-β1/Smad3 Signaling Pathway in a Rabbit Model of Chronic Heart Failure

Zhang

Dang

et al. 2016

Cell Physiol Biochem

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Backgroun/Aims: To explore the effect of cardiac contractility modulation (CCM) on myocardial fibrosis in heart failure and to investigate the underlying mechanism. Methods: Rabbits were randomly divided into sham group, HF group and CCM group. A rabbit model of chronic heart failure (CHF) was induced 12 weeks after aortic constriction by pressure unloading. Then cardiac contractility modulation was delivered to the myocardium lasting six hours per day for 4 weeks. Histology examination was carried out to evaluate the myocardial pathological changes. Protein levels of collagen I, collagen III, α-SMA, MMP2, MMP9, TIMP1, TGF-β1 and Smad3 were measured by western blot analysis. Results: Histology examination results showed that CCM therapy attenuated myocardial fibrosis and collagen deposition in rabbits with CHF. In addition, protein levels of collagen I, collagen III, α-SMA, MMP2, MMP9, TIMP1, TGF-β1 and Smad3 were down regulated. Conclusion: CCM therapy exerted protective effects against myocardial fibrosis potentially by inhibiting TGF-β1/Smad3 signaling pathway in CHF rabbits.

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“…When people with isolated systolic hypertension were compared with healthy subjects, an increased serum MMP 9 activity was found and the elevated levels were able to predict aortic stiffness (Yasmin et al 2005). A study that included 29 patients with acute myocardial infarction showed an association between elevated serum level of pro-MMP 9 and preserved left-ventricular volumes, whereas elevated MMP 2 was found to be a prognostic marker for ventricular remodeling six months after the ischemic event (Cogni et al 2013). Also, the increased serum levels of MMP 9 in people with chronic Chagas cardiomyopathy were demonstrated to be associated with the severity of cardiac impairment (Bautista-López et al 2013).…”

Section: Discussionmentioning

confidence: 99%

“…In people with acute myocardial infarction, an increase of 39% in the probability of ventricular remodeling was reported for each elevation of one unit in MMP 2 level (Cogni et al 2013). This substance behaves in a similar fashion when other tissues undergo either pathological or physiological remodeling (Navarro et al 2006, Morales et al 2007.…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinases 2 and 9 in rabbits with doxorubicin-induced cardiomyopathy

et al. 2018

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RESUMO.-[Metaloproteinases de matriz 2 e 9 em coelhos com cardiomiopatia induzida pela doxorrubicina.] Alguns estudos já demonstraram o papel exercido pelas metaloproteinases de matriz e seus inibidores na cardiotoxicidade promovida pela doxorrubicina. Assim, este estudo teve como objetivo investigar o comportamento das MMPs 2 e 9 plasmáticas e miocárdicas em coelhos com cardiomiopatia induzida pela doxorrubicina, buscando determinar se há correlação entre a atividade dessas colagenases e o remodelamento cardíaco. A cardiomiopatia foi induzida pela doxorrubicina aplicada por via intravenosa duas vezes por semana ao longo de seis semanas consecutivas. A atividade plasmática das MMPs e o ecocardiograma foram avaliados no momento basal e aos 15 e 45 dias após a primeira aplicação da doxorrubicina. A atividade miocárdica dessas enzimas foi quantificada em apenas nove coelhos aos 45 dias e os resultados comparados Some studies have shown the role played by matrix metalloproteinases and their inhibitors in doxorubicin cardiotoxicity. In this study, we sought to investigate how plasma and myocardial MMP 2 and 9 perform in rabbits with doxorubicin-induced cardiomyopathy, searching for a correlation between the activity of these collagenases and cardiac remodeling. Cardiomyopathy was induced by doxorubicin given intravenously twice a week for six consecutive weeks. Plasma MMP activity and the echocardiogram were assessed at baseline, and at 15 and 45 days after first injection of doxorubicin. The myocardial activity of these enzymes was solely evaluated in nine rabbits at 45 days, and results were compared with nine healthy controls. We only identified the full-length forms of both MMP 2 and 9 throughout the study. The plasma pro-MMP 2 reduced along the deterioration of cardiac function, while the pro-MMP 9 increased significantly at T45 as compared to baseline and T15. A negative significant correlation was found to exist between the plasma activity of pro-MMP 2 and mitral E-to-mitral septal annular early diastolic velocity ratio, which is an estimate of mean left atrial pressure and congestion. Only pro-MMP 2 was found in myocardial samples, and mean activity of such enzyme was statistically lower than that recorded for healthy controls. Although no active form was documented for either collagenase, the duration of the treatment with doxorubicin played a role in the alteration of plasma pro-forms activity. However, these changes could not be associated with most echocardiographic parameters that are supportive of cardiac remodeling. Matrix metalloproteinases 2 and 9 in rabbits with doxorubicin-induced cardiomyopathy com outros nove controles saudáveis. Foram identificadas apenas as formas inativas das MMPs 2 e 9 durante todo o estudo. A pro-MMP 2 plasmática reduziu à medida que a função cardiaca se deteriorou, enquanto a pro-MMP 9 aumentou significativamente em T45 quando comparada aos momentos basal e T15. Houve correlação negativa significativa entre a atividade plasmática da pro-MMP 2 e a relação entre E mitral e a ...

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Metalloproteinases-2 and -9 Predict Left Ventricular Remodeling after Myocardial Infarction

Cited by 22 publications

References 36 publications

A N-terminal truncated intracellular isoform of matrix metalloproteinase-2 impairs contractility of mouse myocardium

A N-terminal truncated intracellular isoform of matrix metalloproteinase-2 impairs contractility of mouse myocardium

Cardiac Contractility Modulation Attenuate Myocardial Fibrosis by Inhibiting TGF-β1/Smad3 Signaling Pathway in a Rabbit Model of Chronic Heart Failure

Matrix metalloproteinases 2 and 9 in rabbits with doxorubicin-induced cardiomyopathy

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