Exogenous CXCL4 infusion inhibits macrophage phagocytosis by limiting CD36 signalling to enhance post-myocardial infarction cardiac dilation and mortality.

Cardiovascular Research
Merry L LindseyYonggang Ma

Abstract

Macrophage phagocytosis of dead cells is a prerequisite for inflammation resolution. Because CXCL4 induces macrophage phagocytosis in vitro, we examined the impact of exogenous CXCL4 infusion on cardiac wound healing and macrophage phagocytosis following myocardial infarction (MI). CXCL4 expression significantly increased in the infarct region beginning at Day 3 post-MI, and macrophages were the predominant source. Adult male C57BL/6J mice were subjected to coronary artery occlusion, and MI mice were randomly infused with recombinant mouse CXCL4 or saline beginning at 24 h post-MI by mini-pump infusion. Compared with saline controls, CXCL4 infusion dramatically reduced 7 day post-MI survival [10% (3/30) for CXCL4 vs. 47% (7/15) for saline, P < 0.05] as a result of acute congestive heart failure. By echocardiography, CXCL4 significantly increased left ventricular (LV) volumes and dimensions at Day 5 post-MI (all P < 0.05), despite similar infarct areas compared with saline controls. While macrophage numbers were similar at Day 5 post-MI, CXCL4 infusion increased Ccr4 and Itgb4 and decreased Adamts8 gene levels in the infarct region, all of which linked to CXCL4-mediated cardiac dilation. Isolated Day 5 post-MI macrophages exhibi...Continue Reading

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Citations

Nov 15, 2019·Biochemical Society Transactions·Mavis A A TenkorangMerry L Lindsey
Mar 20, 2019·Basic Research in Cardiology·Lucas BacmeisterDiana Lindner
Nov 20, 2020·Cardiovascular Research·Hongyang ShuDao Wen Wang
Jan 8, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiaji LiuJeffrey J Saucerman
Nov 17, 2020·Current Opinion in Physiology·Ruoshui Li, Nikolaos G Frangogiannis
Oct 31, 2020·Cellular Signalling·Michael J DasekeMerry L Lindsey
Jun 16, 2021·Expert Opinion on Therapeutic Targets·Jan F C GlatzJoost J F P Luiken
Jun 19, 2021·Journal of Molecular and Cellular Cardiology·Akihiko KubotaHiroshi Nakajima
Jan 29, 2022·American Journal of Physiology. Heart and Circulatory Physiology·Mediha Becirovic-AgicMerry L Lindsey

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