Endothelial repair is dependent on CD11c+ leukocytes to establish regrowing endothelial sheets with high cellular density

[摘要] Endothelial injury makes the vessel wall vulnerable to cardiovascular diseases. Injured endothelium regenerates by collective sheet migration, that is, the endothelial cells coordinate their motion and regrow as a sheet of cells with retained cell‐cell contacts into the wounded area. Leukocytes appear to be involved in endothelial repair in vivo; however, little is known about their identity and role in the reparative sheet migration process. To address these questions, we developed a high‐quality en face technique that enables visualizing of leukocytes and endothelial cells simultaneously following an endoluminal scratch wound injury of the mouse carotid artery. We discovered that regrowing endothelium forms a broad proliferative front accompanied by CD11c⁺ leukocytes. Functionally, the leukocytes were dispensable for the initial migratory response of the regrowing endothelial sheet, but critical for the subsequent formation and maintenance of a front zone with high cellular density. Marker expression analyses, genetic fate mapping, phagocyte targeting experiments, and mouse knock‐out experiments indicate that the CD11c⁺ leukocytes were mononuclear phagocytes with an origin from both Ly6C^high and Ly6C^low monocytes. In conclusion, CD11c⁺ mononuclear phagocytes are essential for a proper endothelial regrowth following arterial endoluminal scratch injury. Promoting the endothelial‐preserving function of CD11c⁺ leukocytes may be a strategy to enhance endothelial repair following surgical and endovascular procedures.

[学科分类] 生理学

[关键词] injury;repair