The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions.
The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions.
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DOI：
10.1084/jem.20070885
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发表时间：
2007-11-26
期刊：
影响因子：
--
通讯作者：
Pittet MJ
中科院分区：
文献类型：
--
作者：
Nahrendorf M;Swirski FK;Aikawa E;Stangenberg L;Wurdinger T;Figueiredo JL;Libby P;Weissleder R;Pittet MJ
心肌梗死（MI）的愈合需要单核细胞/巨噬细胞。这些单核吞噬细胞可能降解释放的大分子，并帮助清除死亡的心肌细胞，同时介导肉芽组织形成和重塑。协调这种不同功能的机制仍然未知。鉴于对循环单核细胞异质性的高度评价，我们研究了不同的单核细胞亚群是否以特定的方式对小鼠MI的心肌缺血性损伤起作用。我们确定了MI后单核细胞参与的两个不同阶段，并提出了一个模型，调和这些细胞在愈合中的不同特性。缺血心脏随着时间的推移调节其趋化因子表达谱，并且它们分别通过CCR 2和CX 3CR 1顺序地和主动地募集Ly-6Chi和-6Clo单核细胞。Ly-6Chi单核细胞在早期（I期）占主导地位，并表现出吞噬、蛋白水解和炎症功能。Ly-6Clo单核细胞在晚期（II期）占主导地位，具有减弱的炎症特性，并表达血管内皮生长因子。因此，Ly-6Chi单核细胞消化受损组织，而Ly-6Clo单核细胞通过肌成纤维细胞积累、血管生成和胶原沉积促进愈合。患有慢性Ly-6Chi单核细胞增多症的动脉粥样硬化小鼠的MI导致愈合受损，强调需要平衡和协调的反应。这些观察结果为调节缺血性损伤反应的细胞和分子事件提供了新的机制见解，并确定了可以影响MI后愈合和心室重塑的新治疗靶点。
Healing of myocardial infarction (MI) requires monocytes/macrophages. These mononuclear phagocytes likely degrade released macromolecules and aid in scavenging of dead cardiomyocytes, while mediating aspects of granulation tissue formation and remodeling. The mechanisms that orchestrate such divergent functions remain unknown. In view of the heightened appreciation of the heterogeneity of circulating monocytes, we investigated whether distinct monocyte subsets contribute in specific ways to myocardial ischemic injury in mouse MI. We identify two distinct phases of monocyte participation after MI and propose a model that reconciles the divergent properties of these cells in healing. Infarcted hearts modulate their chemokine expression profile over time, and they sequentially and actively recruit Ly-6Chi and -6Clo monocytes via CCR2 and CX3CR1, respectively. Ly-6Chi monocytes dominate early (phase I) and exhibit phagocytic, proteolytic, and inflammatory functions. Ly-6Clo monocytes dominate later (phase II), have attenuated inflammatory properties, and express vascular–endothelial growth factor. Consequently, Ly-6Chi monocytes digest damaged tissue, whereas Ly-6Clo monocytes promote healing via myofibroblast accumulation, angiogenesis, and deposition of collagen. MI in atherosclerotic mice with chronic Ly-6Chi monocytosis results in impaired healing, underscoring the need for a balanced and coordinated response. These observations provide novel mechanistic insights into the cellular and molecular events that regulate the response to ischemic injury and identify new therapeutic targets that can influence healing and ventricular remodeling after MI.
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影响因子：
15.9
作者：
LIBBY, P;MAROKO, PR;BRAUNWALD, E
通讯作者：
BRAUNWALD, E
影响因子：
37.8
作者：
Leor, Jonathan;Rozen, Liat;Danon, David
通讯作者：
Danon, David
DOI：
10.1016/s0735-1097(01)01721-1
发表时间：
2002-01-16
影响因子：
24
作者：
Maekawa, Y;Anzai, T;Ogawa, S
通讯作者：
Ogawa, S
在动脉粥样硬化之前和开发过程中淋巴细胞募集到主动脉壁是部分依赖性L-选择蛋白。
DOI：
10.1084/jem.20052205
发表时间：
2006-05-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.8
作者：
Kirtane, AJ;Bui, A;Gibson, CM
通讯作者：
Gibson, CM