2021年7月27日，美国华盛顿大学Kory J. Lavine课题组在《免疫》杂志发表论文。该研究发现，常驻心脏巨噬细胞介导适应性心肌重塑。

研究人员表示，心脏巨噬细胞是一个异质性的细胞群，具有不同的起源、动态和功能。最近的研究显示，来自浸润性单核细胞的C-C化学因子受体2阳性（CCR2⁺）巨噬细胞调节着心肌炎症和心衰的发病机制。相对而言，人们对组织常驻（CCR2^-）巨噬细胞的功能知之甚少。

研究人员确定了CCR2^-巨噬细胞在慢性衰竭的心脏中的重要作用。扩张型心肌病小鼠体内CCR2^-巨噬细胞的耗尽加速了死亡率，并损害了心室重塑和冠状动脉血管生成，这是在心脏收缩力下降的情况下维持心输出量所必需的适应性变化。从机制上讲，CCR2^-巨噬细胞通过局部粘附复合物与邻近的心肌细胞相互作用，并通过控制生长因子表达的TRPV4（transient receptorpotential vanilloid 4）依赖性途径在机械拉伸时被激活。这些发现确立了组织驻留的巨噬细胞在适应性心脏重塑中的作用，并暗示了机械感应在心脏巨噬细胞激活中的作用。

附：英文原文

Title: Resident cardiac macrophages mediate adaptive myocardial remodeling

Author: Nicole R. Wong, Jay Mohan, Benjamin J. Kopecky, Shuchi Guo, Lixia Du, Jamison Leid, Guoshuai Feng, Inessa Lokshina, Oleksandr Dmytrenko, Hannah Luehmann, Geetika Bajpai, Laura Ewald, Lauren Bell, Nikhil Patel, Andrea Bredemeyer, Carla J. Weinheimer, Jessica M. Nigro, Attila Kovacs, Sachio Morimoto, Peter O. Bayguinov, Max.R. Fisher, W. Tom Stump, Michael Greenberg, James A.J. Fitzpatrick, Slava Epelman, Daniel Kreisel, Rajan Sah, Yongjian Liu, Hongzhen Hu, Kory J. Lavine

Issue&Volume: 2021-07-27

Abstract: Cardiac macrophages represent a heterogeneous cell population with distinct origins,dynamics, and functions. Recent studies have revealed that C-C Chemokine Receptor2 positive (CCR2+) macrophages derived from infiltrating monocytes regulate myocardial inflammationand heart failure pathogenesis. Comparatively little is known about the functionsof tissue resident (CCR2) macrophages. Herein, we identified an essential role for CCR2 macrophages in the chronically failing heart. Depletion of CCR2 macrophages in mice with dilated cardiomyopathy accelerated mortality and impairedventricular remodeling and coronary angiogenesis, adaptive changes necessary to maintaincardiac output in the setting of reduced cardiac contractility. Mechanistically, CCR2 macrophages interacted with neighboring cardiomyocytes via focal adhesion complexesand were activated in response to mechanical stretch through a transient receptorpotential vanilloid 4 (TRPV4)-dependent pathway that controlled growth factor expression.These findings establish a role for tissue-resident macrophages in adaptive cardiacremodeling and implicate mechanical sensing in cardiac macrophage activation.

DOI: 10.1016/j.immuni.2021.07.003

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00289-2