Inhibiting matrix metalloproteinase-2 reduces protein release into coronary effluent from isolated rat hearts during ischemia-reperfusion

Fert-Bober, Justyna; León, Hernando; Sawicka, Jolanta; Basran, Rashpal; Devon, Richard M.; Schulz, Richard; Sawicki, Grzegorz

doi:10.1007/s00395-008-0727-y

Cited by 53 publications

(47 citation statements)

References 42 publications

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“…This is the first demonstration that the cardioprotective dose ranges of ilomastat, when administered before ischemia or before reperfusion, were not overlapping in vivo. Our present results are supported by previous studies describing that cardiac mechanical function after ischemia/reperfusion injury via the inhibition of MMP-2 in isolated rat hearts [25,78,79]. We have recently shown that the intravenously injected ilomasat (at 1.5 µmol/kg, administered before the onset of ischemia) decreased infarct size and had a comparable cardioprotective effect to ischemic late preconditioning [36].…”

Section: Study 1: Mmp-2 Inhibition By Ilomasat Exerts Cardioprotectionsupporting

confidence: 91%

Cytoprotective approaches to protect myocardium against ischemia/reperfusion injury

Pálóczi¹

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Section: Study 1: Mmp-2 Inhibition By Ilomasat Exerts Cardioprotectionsupporting

confidence: 91%

Cytoprotective approaches to protect myocardium against ischemia/reperfusion injury

Pálóczi¹

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“…This suggests that important role in mechanisms of cardioprotection induced by these different forms of short-term adaptation procedures plays the observed reduction of MMP-2 activities at the beginning of test ischemia. Inhibition of MMP using inhibitors may provide benefits in the treatment of cardiac diseases through protecting cardiac myocytes and also by protecting the integrity of endothelium and possibly intracellular membranes (Fert-Bober et al 2008). To the significant role of MMP-2 in processes associated with I/R point our data showing the time-dependent changes of MMP-2 activities during prolonged ischemia and release of the active enzyme into the effluent during the following reperfusion.…”

Section: Discussionmentioning

confidence: 72%

Influence of ischemia/reperfusion and modulation of PI3K/Akt kinase pathway on matrix metalloproteinase-2 in rat hearts

Špániková¹,

Ivanová²,

Matějíková³

et al. 2010

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Abstract. Matrix metalloproteinases (MMPs) are enzymes that play an important role in degradation and remodeling of extracellular matrix and MMP-2 has been also shown as a primary mediator of the acute mechanical dysfunction of the heart immediately after ischemia/reperfusion (I/R). The aims of the study were to investigate the influence of I/R on MMP-2 and to study the effects of wortmannin on modulation of MMP-2 activities after cycle of short I/R procedures (ischemic preconditioning, IP). Wortmannin is a specific inhibitor of PI3K/Akt kinase pathway activation of which was found to play a role in infarct size limiting mechanisms in the rat heart. In the study isolated Langendorff-perfused rat hearts subjected to protocols of prolonged (test) I/R and/or IP were used. Wortmannin was infused before and during the reperfusion phase of IP. The levels and activation of proteins were determined by immunoblot assay. The MMP-2 activities were measured by zymography. We found that ischemia induced time-dependent activation of tissue pro-MMP-2. Strong activation occurred after 15 min ischemia, during prolonged ischemia and following reperfusion the activities of this form of MMP-2 declined. The specific activities of both 72 and 63 kDa forms of MMP-2 were increased in perfusates collected during reperfusion after 30 min ischemia and these activities peaked in the first minute of reperfusion. Cycle of short ischemia and reperfusion that led to increased cardiac tolerance against prolonged I/R reduced 72 kDa MMP-2 activities and induced also an activation of Akt kinase. The application of wortmannin was connected with inhibition of IP-mediated Akt kinase activation. Moreover, the actions of wortmannin were linked with modulation of MMP-2 activities. Our results suggest that MMP-2 may be involved in the responses of rat hearts to ischemia and point to possible relationship between Akt kinase and modulation of MMP-2 activities in rat hearts.

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“…In one study, a 97% decrease in the ratio of oxidized:reduced glutathione, an indicator of reduced oxidative stress, was observed after minocycline treatment [174]. The positive effects of doxycycline on both cardiac function and tissue damage have also been observed in in vitro ischemiareperfusion studies using isolated perfused rat hearts [177,178].…”

Section: Myocardial Infarction and Cardiovascular Diseasementioning

confidence: 89%

Anti-Inflammatory Activity of Tetracyclines: Applications to Human Disease

Higgins¹

2011

aiaaamc

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Tetracyclines possess anti-inflammatory characteristics which are largely independent of their antibacterial activity. A variety of in vitro biologic effects have been reported for tetracyclines in both immune and non-immune cells. The in vivo therapeutic efficacy of tetracyclines in diseases such as rheumatoid arthritis, multiple sclerosis, and stroke has also been demonstrated in both animal models and clinical studies. This review describes the experimental evidence which demonstrates the various non-antibacterial anti-inflammatory activities of tetracyclines and discusses possible mechanisms of action of these drugs.

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Inhibiting matrix metalloproteinase-2 reduces protein release into coronary effluent from isolated rat hearts during ischemia-reperfusion

Abstract: MMP inhibition not only reduces cardiac mechanical dysfunction but also reduces endothelial damage resulting from cardiac I/R injury.

Cited by 53 publications

References 42 publications

Cytoprotective approaches to protect myocardium against ischemia/reperfusion injury

Cytoprotective approaches to protect myocardium against ischemia/reperfusion injury

Influence of ischemia/reperfusion and modulation of PI3K/Akt kinase pathway on matrix metalloproteinase-2 in rat hearts

Anti-Inflammatory Activity of Tetracyclines: Applications to Human Disease

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