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

Autor: Pluijmert NJ; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands., de Jong RCM; Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands., de Vries MR; Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands., Pettersson K; Athera Biotechnologies, Stockholm, Sweden., Atsma DE; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands., Jukema JW; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands., Quax PHA; Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2021 Aug; Vol. 25 (16), pp. 7772-7782. Date of Electronic Publication: 2021 Jun 30.
DOI: 10.1111/jcmm.16662
Abstrakt: 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.
(© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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