C-Reactive Protein and Complement Are Important Mediators of Tissue Damage in Acute Myocardial Infarction

TLDR

Myocardial infarction triggers an acute phase response with deposition of C‑reactive protein and complement in the infarct, and higher peak CRP levels predict worse post‑infarct outcomes. In rats, human CRP injection after coronary ligation enlarged infarct size by ~40 %, an effect completely blocked by complement depletion, which also reduced infarct size when given up to 2 h post‑ligation, confirming CRP and complement as key mediators and therapeutic targets.

Abstract

Myocardial infarction in humans provokes an acute phase response, and C-reactive 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 binds to damaged cells and activates complement, but rat CRP does not activate complement. Here we show that injection of human CRP into rats after ligation of the coronary artery reproducibly enhanced infarct size by approximately 40%. In vivo complement depletion, produced by cobra venom factor, completely abrogated this effect. Complement depletion also markedly reduced infarct size, even when initiated up to 2 h after coronary ligation. These observations demonstrate that human CRP and complement activation are major mediators of ischemic myocardial injury and identify them as therapeutic targets in coronary heart disease.