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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Attenuation of myocardial reperfusion injury in pigs by Mirococept, a membrane-targeted complement inhibitor derived from human CR1
Cardiovascular Research, Volume 76, No. 3, Year 2007
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Description
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. © 2007 European Society of Cardiology.
Authors & Co-Authors
Banz, Yara
Switzerland, Bern
University of Bern
United States, Boston
Beth Israel Deaconess Medical Center
Robson, Simon Christopher
United States, Boston
Beth Israel Deaconess Medical Center
Csizmadia, Eva
United States, Boston
Beth Israel Deaconess Medical Center
Meier, Pascal Pascal
Switzerland, Bern
Swiss Cardiovascular Center, University Hospital Bern
Smith, Richard Alan G.
Unknown Affiliation
Rieben, Robert
Switzerland, Bern
University of Bern
Statistics
Citations: 34
Authors: 6
Affiliations: 3
Identifiers
Doi:
10.1016/j.cardiores.2007.07.016
ISSN:
00086363
Research Areas
Cancer
Noncommunicable Diseases
Violence And Injury