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

Autor: Douwe E. Atsma, J. Wouter Jukema, Rob C. M. de Jong, Margreet R. de Vries, Niek J. Pluijmert, Paul H.A. Quax, Knut Pettersson
Přispěvatelé: Cardiology
Rok vydání: 2021
Předmět:
Zdroj: Journal of Cellular and Molecular Medicine
Journal of Cellular and Molecular Medicine, 25(16), 7772-7782. WILEY
Journal of Cellular and Molecular Medicine, 25(16), 7772-7782. Wiley-Blackwell
Pluijmert, N J, de Jong, R C M, de Vries, M R, Pettersson, K, Atsma, D E, Jukema, J W & Quax, P H A 2021, ' Phosphorylcholine antibodies restrict infarct size and left ventricular remodelling by attenuating the unreperfused post-ischaemic inflammatory response ', Journal of Cellular and Molecular Medicine, vol. 25, no. 16, pp. 7772-7782 . https://doi.org/10.1111/jcmm.16662
ISSN: 1582-4934
1582-1838
DOI: 10.1111/jcmm.16662
Popis: 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.
Databáze: OpenAIRE