Phosphorylcholine antibodies restrict infarct size and left ventricular remodelling by attenuating the unreperfused post‐ischaemic inflammatory response

Abstract

Phosphorylcholine is a pro‐inflammatory epitope exposed on apoptotic cells, and phosphorylcholine monoclonal immunoglobulin (Ig)G antibodies (PC‐mAb) have anti‐inflammatory properties. In this study, we hypothesize that PC‐mAb treatment reduces adverse cardiac remodelling and infarct size (IS) following unreperfused transmural myocardial infarction (MI). Unreperfused MI was induced by permanent ligation of the left anterior descending (LAD) coronary artery in hypercholesterolaemic APOE*3‐Leiden mice. Three weeks following MI, cardiac magnetic resonance (CMR) imaging showed a reduced LV end‐diastolic volume (EDV) by 21% and IS by 31% upon PC‐mAb treatment as compared to the vehicle control group. In addition, the LV fibrous content was decreased by 27% and LV wall thickness was better preserved by 47% as determined by histological analysis. Two days following MI, CCL2 concentrations, assessed by use of ELISA, were decreased by 81% and circulating monocytes by 64% as assessed by use of FACS analysis. Additionally, local leucocyte infiltration determined by immunohistological analysis showed a 62% decrease after three weeks. In conclusion, the local and systemic inflammatory responses are limited by PC‐mAb treatment resulting in restricted adverse cardiac remodelling and IS following unreperfused MI. This indicates that PC‐mAb holds promise as a therapeutic agent following MI limiting adverse cardiac remodelling.

Inflammation and Oxidative Stress Role of S100A12 as a Potential Diagnostic and Therapeutic Biomarker in Acute Myocardial Infarction

“…AMI can lead to cardiomyocyte death, often followed by a robust inflammatory response in myocardial tissue. Previous studies have demonstrated that the activation of complement and Toll-like receptor (TLR)/interleukin-1 (IL-1) signaling is involved in the onset and development of inflammation [12][13][14]. A suitable inflammatory response is beneficial for the healing of injured myocardial tissue, indicating that the body performs the function of self-repair.…”

Phosphorylcholine Monoclonal Antibody Therapy Decreases Intraplaque Angiogenesis and Intraplaque Hemorrhage in Murine Vein Grafts

“…The IgG PC-mAb is also able to block oxLDL uptake by macrophages unlike the T15/E06 based IgG and binds late apoptotic cells, but not normal or ‘early’ apoptotic cells [ 3 ]. We recently showed that PC-mAb prevented macrophage influx after myocardial infarction via reduced systemic inflammatory responses [ 34 , 35 ].…”