Activities of cardiac tissue matrix metalloproteinases 2 and 9 are reduced by remote ischemic preconditioning in cardiosurgical patients with cardiopulmonary bypass

Abstract

BackgroundTransient episodes of ischemia in a remote organ or tissue (remote ischemic preconditioning, RIPC) can attenuate myocardial injury. Myocardial damage is associated with tissue remodeling and the matrix metalloproteinases 2 and 9 (MMP-2/9) are crucially involved in these events. Here we investigated the effects of RIPC on the activities of heart tissue MMP-2/9 and their correlation with serum concentrations of cardiac troponin T (cTnT), a marker for myocardial damage.MethodsIn cardiosurgical patients with cardiopulmonary bypass (CPB) RIPC was induced by four 5 minute cycles of upper limb ischemia/reperfusion. Cardiac tissue was obtained before as well as after CPB and serum cTnT concentrations were measured. Tissue derived from control patients (N = 17) with high cTnT concentrations (≥0.32 ng/ml) and RIPC patients (N = 18) with low cTnT (≤0.32 ng/ml) was subjected to gelatin zymography to quantify MMP-2/9 activities.ResultsIn cardiac biopsies obtained before CPB, activities of MMP-2/9 were attenuated in the RIPC group (MMP-2: Control, 1.13 ± 0.13 a.u.; RIPC, 0.71 ± 0.12 a.u.; P < 0.05. MMP-9: Control, 1.50 ± 0.16 a.u.; RIPC, 0.87 ± 0.14 a.u.; P < 0.01), while activities of the pro-MMPs were not altered (P > 0.05). In cardiac biopsies taken after CPB activities of pro- and active MMP-2/9 were not different between the groups (P > 0.05). Spearman’s rank tests showed that MMP-2/9 activities in cardiac tissue obtained before CPB were positively correlated with postoperative cTnT serum levels (MMP-2, P = 0.016; MMP-9, P = 0.015).ConclusionsActivities of MMP-2/9 in cardiac tissue obtained before CPB are attenuated by RIPC and are positively correlated with serum concentrations of cTnT. MMPs may represent potential targets for RIPC mediated cardioprotection.Trial registrationClinicalTrials.gov identifier NCT00877305.

Effect of remote ischemic preconditioning on left atrial remodeling and prothrombotic response after radiofrequency catheter ablation for atrial fibrillation

“…Remote ischemic preconditioning (RIPC), a noninvasive, simple procedure, can help a distant organ or tissue to withstand subsequent prolonged ischemic events with brief episodes of nonlethal ischemia . Previous clinical trials have shown that RIPC might attenuate cardiac tissue remodeling in patients undergoing cardiovascular surgery and chronic heart failure after myocardial infarction . Stazi et al .…”

Profiling of cell stress protein expression in cardiac tissue of cardiosurgical patients undergoing remote ischemic preconditioning: implications for thioredoxin in cardioprotection

“…The study was performed in accordance with the fourth revision of the Declaration of Helsinki (1996) and is registered at ClinicalTrials.gov (NCT00877305). Employing patient sera and biopsy material, two experimental sub-studies have been published recently ([ 26 , 27 ]; Additional file 1 : Table S1).…”

“…Aim of the study was to identify cell stress associated proteins in cardiac tissue samples of cardiosurgical patients with and without RIPC and patients included into the study were selected based on the criteria described earlier [ 26 ]. Each patient (age ≥ 18 years) gave written informed consent to participate in the study.…”

“…Demographic data, information regarding the comorbidities, medications and ICU (intensive care unit) data of the patients employed in the clinical trial and experimental sub-studies (NCT00877305) have been presented recently [ 26 , 27 ]. Cardiac tissue of the right atrium was collected from RIPC and control patients before as well as after CPB.…”

“…Despite the advances in the clinical application of RIPC and increasing knowledge concerning the RIPC-released humoral factors and induced signalling events, there is still an apparent lack of information regarding the proteins that are regulated by RIPC within the myocardial tissue [ 24 , 25 ]. We have recently shown that the activities of matrix metalloproteinases 2 and 9 (MMP-2/9) as well as the expression levels of procaspase-3 and enzymatic activities of myeloperoxidase are increased in heart tissue of cardiosurgical patients receiving RIPC [ 26 , 27 ]. However, the precise cellular mechanisms that are responsible for the RIPC-mediated cardioprotection are still unclear and discussed controversially.…”