Resident cardiac macrophages mediate adaptive myocardial remodeling.
Resident cardiac macrophages mediate adaptive myocardial remodeling.
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常驻心脏巨噬细胞介导适应性心肌重塑。
DOI：
10.1016/j.immuni.2021.07.003
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发表时间：
2021-09-14
期刊：
影响因子：
32.4
通讯作者：
Lavine KJ
中科院分区：
文献类型：
--
作者：
Wong NR;Mohan J;Kopecky BJ;Guo S;Du L;Leid J;Feng G;Lokshina I;Dmytrenko O;Luehmann H;Bajpai G;Ewald L;Bell L;Patel N;Bredemeyer A;Weinheimer CJ;Nigro JM;Kovacs A;Morimoto S;Bayguinov PO;Fisher MR;Stump WT;Greenberg M;Fitzpatrick JAJ;Epelman S;Kreisel D;Sah R;Liu Y;Hu H;Lavine KJ
心脏巨噬细胞代表了具有不同起源、动力学和功能的异质细胞群体。最近的研究表明，来源于浸润单核细胞的C-C趋化因子受体2阳性（CCR 2+）巨噬细胞调节心肌炎症和心力衰竭发病机制。相对而言，对组织驻留（CCR 2 −）巨噬细胞的功能知之甚少。在此，我们确定了CCR 2-巨噬细胞在慢性心力衰竭中的重要作用。扩张型心肌病小鼠中CCR 2 −巨噬细胞的消耗加速了死亡率，并损害了心室重塑和冠状动脉血管生成，这是在心脏收缩力降低的情况下维持心输出量所必需的适应性变化。从机制上讲，CCR 2 −巨噬细胞通过粘着斑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瞬时受体电位香草酸4（TRPV 4）依赖性途径响应机械拉伸而被激活。这些发现确立了组织驻留巨噬细胞在适应性心脏重塑中的作用，并涉及心脏巨噬细胞激活中的机械传感。常驻心脏巨噬细胞是心脏发育和稳态的关键调节因子，然而，这些细胞在疾病期间的作用目前尚不清楚。Wong，Mohan，Kopecky等人揭示了驻留的心脏巨噬细胞通过TRPV 4依赖性机制感知机械刺激来协调衰竭心脏的适应性重塑和存活。
Cardiac macrophages represent a heterogeneous cell population with distinct origins, dynamics, and functions. Recent studies have revealed that C-C Chemokine Receptor 2 positive (CCR2+) macrophages derived from infiltrating monocytes regulate myocardial inflammation and heart failure pathogenesis. Comparatively little is known about the functions of 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 impaired ventricular remodeling and coronary angiogenesis, adaptive changes necessary to maintain cardiac output in the setting of reduced cardiac contractility. Mechanistically, CCR2− macrophages interacted with neighboring cardiomyocytes via focal adhesion complexes and were activated in response to mechanical stretch through a transient receptor potential vanilloid 4 (TRPV4) dependent pathway that controlled growth factor expression. These findings establish a role for tissue resident macrophages in adaptive cardiac remodeling and implicate mechanical sensing in cardiac macrophage activation. Resident cardiac macrophages are key regulators of heart development and homeostasis, however, the role of these cells during disease is presently unclear. Wong, Mohan, Kopecky et al. reveal that resident cardiac macrophages orchestrate adaptive remodeling and survival of the failing heart by sensing mechanical stimuli through a TRPV4 dependent mechanism.
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DOI：
10.1073/pnas.1300290110
发表时间：
2013-06-04
影响因子：
11.1
作者：
Godwin, James W.;Pinto, Alexander R.;Rosenthal, Nadia A.
通讯作者：
Rosenthal, Nadia A.
影响因子：
11.8
作者：
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DOI：
10.1152/ajplung.00315.2009
发表时间：
2010-09-01
影响因子：
4.9
作者：
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通讯作者：
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影响因子：
20.3
作者：
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影响因子：
14.8
作者：
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