Attenuation of myocardial reperfusion injury in pigs by Mirococept, a membrane-targeted complement inhibitor derived from human CR1

Banz, Yara; Hess, Otto M; Robson, Simon C; Csizmadia, Eva; Mettler, Daniel; Meier, Pascal; Haeberli, André; Shaw, Sidney; Smith, Richard A; Rieben, Robert (2007). Attenuation of myocardial reperfusion injury in pigs by Mirococept, a membrane-targeted complement inhibitor derived from human CR1. Cardiovascular research, 76(3), pp. 482-93. Oxford: Elsevier Ltd. 10.1016/j.cardiores.2007.07.016

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OBJECTIVES: Membrane-targeted application of complement inhibitors may ameliorate ischemia/reperfusion (I/R) injury by directly targeting damaged cells. We investigated whether Mirococept, a membrane-targeted, myristoylated peptidyl construct derived from complement receptor 1 (CR1) could attenuate I/R injury following acute myocardial infarction in pigs. METHODS: In a closed-chest pig model of acute myocardial infarction, Mirococept, the non-tailed derivative APT154, or vehicle was administered intracoronarily into the area at risk 5 min pre-reperfusion. Infarct size, cardiac function and inflammatory status were evaluated. RESULTS: Mirococept targeted damaged vasculature and myocardium, significantly decreasing infarct size compared to vehicle, whereas APT154 had no effect. Cardioprotection correlated with reduced serum troponin I and was paralleled by attenuated local myocardial complement deposition and tissue factor expression. Myocardial apoptosis (TUNEL-positivity) was also reduced with the use of Mirococept. Local modulation of the pro-inflammatory and pro-coagulant phenotype translated to improved left ventricular end-diastolic pressure, ejection fraction and regional wall motion post-reperfusion. CONCLUSIONS: Local modification of a pro-inflammatory and pro-coagulant environment after regional I/R injury by site-specific application of a membrane-targeted complement regulatory protein may offer novel possibilities and insights into potential treatment strategies of reperfusion-induced injury.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Thromboselabor Kinderklinik (discontinued)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Tiefenau Hospital (discontinued) > Forschungsgruppe Vasoaktive Peptide (discontinued)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Herz und Gefässe

UniBE Contributor:

Hess, Otto; Haeberli, André; Shaw, Sidney and Rieben, Robert

ISSN:

0008-6363

ISBN:

17825275

Publisher:

Elsevier Ltd.

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:55

Last Modified:

27 Apr 2018 09:14

Publisher DOI:

10.1016/j.cardiores.2007.07.016

PubMed ID:

17825275

Web of Science ID:

000251478400014

BORIS DOI:

10.7892/boris.23244

URI:

https://boris.unibe.ch/id/eprint/23244 (FactScience: 40692)

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