Splenic Marginal Zone B Lymphocytes Regulate Cardiac Remodeling After Acute Myocardial Infarction in Mice.

Background: Mature B lymphocytes alter the recovery of cardiac function after acute myocardial infarction (MI) in mice. Follicular B cells and marginal zone B (MZB) cells are spatially distinct mature B-cell populations in the spleen, and they exert specific functional properties. microRNA-21 (miR21)/hypoxia-inducible factor-α (HIF-α)-related pathways have been shown to govern B-cell functions.
Objectives: The goal of this study was to unravel the distinct role of MZB cells and that of endogenous activation of miR21/HIF-α signaling in MZB cells during post-ischemic injury.
Methods: Acute MI was induced in mice by permanent ligation of the left anterior descending coronary artery. Cardiac function and remodeling were assessed by using echocardiography and immunohistochemistry. To determine the specific role of MZB cells, the study used mice with B-cell lineage-specific conditional deletion of Notch signaling, which leads to selection deficiency of MZB cells. To evaluate the role of the HIF-1α isoform, mice were generated with MZB-cell lineage-specific conditional deletion of Hif1a.
Results: Acute MI prompted an miR21-dependent increase in HIF-1α, particularly in splenic MZB cells. MZB cell deficiency and MZB cell-specific deletion of miR21 or Hif1a improved cardiac function after acute MI. miR21/HIF-1α signaling in MZB cells was required for Toll-like receptor dependent expression of the monocyte chemoattractant protein CCL7, leading to increased mobilization of inflammatory monocytes to the ischemic myocardium and to adverse post-ischemic cardiac remodeling.
Conclusions: This work reveals a novel function for the miR21/HIF-1α pathway in splenic MZB cells with potential major implications for the modulation of cardiac function after acute MI.
Competing Interests: Funding Support and Author Disclosures This work was supported by Fondation pour la Recherche Médicale (DEQ20160334910, Prof Silvestre; FDT20160435312, Prof Zlatanova), Fondation de France (FDF 00066471, Profs Silvestre and Pinto), Fédération Française de Cardiologie (Profs Silvestre and Sun) China Scholarship Council (No. 201708310220, Prof Sun) French National Research Agency (ANR to Prof Silvestre), and institutional grants from Université de Paris and the French National Institute for Health and Medical Research. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)