Abstract 18513: CXCl16 Promotes Ly6Chigh Monocyte/Macrophage Infiltration and Impairs Cardiac Function After Acute Myocardial Infarction
Objective: CXCL16 has been implicated in the pathogenesis of atherosclerosis, but the function of CXCL16 in myocardial infarction (MI) is unknown. This research examines the effects of CXCL16 in myocardial infarcted mice.
Methods and results: MI was induced in 8 to 12 week-old male mice (C57BL/6 background) by permanent coronary ligation of the left anterior descending artery (LAD). The expression of CXCL16 was increased in the heart of mice after MI on day 1. Compared to WT mice, CXCL16 knockout (CXCL16 KO) mice showed improved cardiac function by echocardiography and attenuated infarct size by Masson trichrome staining on 14 days after MI. FACS analysis of cardiac tissue of mice on 3 days after MI showed an increased infiltration of CD45+CD11b+F4/80+ monocytes/macrophages, including Ly6Chigh monocytes/macrophages and Ly6Clow monocytes/macrophages. Q-PCR analysis demonstrated that TNFα and IL1β were highly expressed in Ly6Chigh monocytes/macrophages, while IL4 and TGFβ were highly expressed in Ly6Clow monocytes/macrophages. Compared to WT mice, CXCL16 KO mice showed a decreased infiltration of Ly6Chigh monocytes/macrophages into infarcted myocardium 3 days post MI. There was no significant difference in the infiltration of Ly6Clow monocytes/macrophages between WT and CXCL16 KO mice. The infiltration of total monocytes/macrophages was reduced in CXCL16 KO mice, probably due to the decreased infiltration of Ly6Chigh monocytes/macrophages. LAD ligated WT mice with neutralizing CXCL16 antibodies displayed significant improvement of cardiac function and decrease of infarct size compared to WT mice.
Conclusions: Our results suggest that following acute myocardial infarction, CXCL16 lead to the recruitment of Ly6Chigh monocytes/macrophages into the injured myocardium and the aggravation of tissue inflammation, which exacerbating cardiac function. Our finding indicates CXCL16 can be a new potential target for myocardial infarction therapy.
Author Disclosures: J. Zhang: None. T. Li: None. Y. Ma: None. J. Zhang: None. J. Du: None.
- © 2016 by American Heart Association, Inc.