During a myocardial ischemic event, acute occlusion sets in motion cell necrosis and myocardial tissue injury referred to as a myocardial ischemic-reperfusion injury (MI/R). One of the leading causes of MI/R injury is the initiation of the complement system. The end product of stimulating major complement components such as C3a or C5a is neutrophil accumulation and deposition in injured myocardium. Therapeutic agents are being investigated to limit the injury caused by complement activation in MI/R injuries. One such novel therapeutic is the use of a recombinant form of cobra venom factor (HC3) that has human homologous modifications.
Cobra venom factor (CVF) is the complement activating protein from cobra venom that resembles C3b. In this study, mice treated with either purified CVF or HC3 were protected from MI/R injury with resultant preservation of cardiac function determined by transthoracic echocardiography. Evans blue staining was used to assess infarct size to area at risk (AAR) and left ventricular tissue area. Mice treated with HC3 had a substantially lower percent of infarct to AAR and left ventricular size than control mice. Immunochemistry staining was performed to assess for complement C3 deposition in the myocardium. Mice treated with HC3 showed minimal complement deposition in the AAR. In contrast, the control group showed heavy C3 deposition in the region of the infarct and of the entire AAR.
These results suggest that, like purified CVF, HC3 causes a downstream signaling and recruitment of the complement convertase component C3/C5, which results in complement depletion and myocardial protection following MI/R. Demonstration of the efficacy of HC3 in mice to preserve cardiac function suggests it may have the potential to be used as a therapeutic in the prevention of human MI/R injuries.
|Advisor:||Steele, Janet, Stahl, Gregory|
|Commitee:||Carlson, Kimberly, Hoback, Wyatt|
|School:||University of Nebraska at Kearney|
|School Location:||United States -- Nebraska|
|Source:||MAI 47/03M, Masters Abstracts International|
|Subjects:||Cellular biology, Physiology|
|Keywords:||Cobra venom factor, Myocardial ischemia-reperfusion injury, Recombinant humanized cobra venom factor|
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