C-reactive protein and complement are important mediators of tissue damagein acute myocardial infarction

Myocardial infarction in humans provokes an acute phase response, and C-rea ctive protein (CRP), the classical acute phase plasma protein, is deposited together with complement within the infarct. The peak plasma CRP value is strongly associated with postinfarct morbidity and mortality. Human CRP bin ds to damaged cells and activates complement, but rat CRP does not activate complement. Here we show that injection of human CRP into rats after ligat ion of the coronary artery reproducibly enhanced infarct size by similar to 40%. In vivo complement depletion, produced by cobra venom factor, complet ely abrogated this effect. Complement depletion also markedly reduced infar ct size, even when initiated up to 2 h after coronary ligation. These obser vations demonstrate that human CRP and complement activation are major medi ators of ischemic myocardial injury and identify them as therapeutic target s in coronary heart disease.