The effect of C-reactive protein deposition on myocardium with ischaemia-reperfusion injury in rats.

We evaluated the effect of monomeric C-reactive protein (CRP) deposition on areas at risk (AAR) of myocardium with ischaemia-reperfusion injury. Myocardial ischaemia-reperfusion injury model was produced by ligation of the left anterior descending coronary artery for 45 min followed by 45 min of reperfusion using female Sprague-Dawley rats. Tissue from non-ischaemic areas, areas at risk and infarct areas determined by Evans blue and 2,3,5-triphenyltetrazolium chloride staining was obtained from the sham group, the ischaemia-reperfusion injury without C-reactive protein (CRP) injection group (I/R only group), and the ischaemia-reperfusion injury with CRP injection group (I/R + CRP group). We assessed the effect of CRP injection on infarct size, CRP deposition, CRP and IL-6 mRNA expression, the third component of complement (C3) immunodeposition and mitochondrial structural remodelling with apoptosis by quantitative RT-PCR analyses, immunohistochemistry, direct immunofluorescence, electron microscopy and Terminal deoxynucleotide transferase dUTP Nick End Labelling assay, respectively. All images were analysed using an automated morphology tool. The infarct area significantly increased in the I/R + CRP group compared to the I/R only group. The anti CRP antibody confirmed that CRP deposition occurred in both the infarct and area at risk (AAR) of the I/R + CRP group. The myocardium did not exhibit CRP mRNA expression, and the CRP treatment group showed a tendency for IL-6 to increase without statistical significance. Activated C3, apoptosis and mitochondrial destruction increased on AAR and infarct area in the I/R + CRP group. These results strongly suggest the active participation of the deposition of CRP on AAR in the progression of myocardial infarction following ischaemia-reperfusion injury, accompanied by complement activation and mitochondrial change.