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

Abstract

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.

Driving regeneration, instead of healing, in adult mammals: the decisive role of resident macrophages through efferocytosis

“…In the AT, CD11c + macrophages have been identified as pro-inflammatory and involved in the clearance of senescent cells 48 , 49 . The expression of CD11c has also been associated with both tissue resident macrophages that play a central role in non-inflammatory apoptotic cells clearance required for the maintenance of tissue homeostasis 50 , 51 and monocyte-derived macrophages involved in tissue repair 52 .…”

Disturbed Laminar Blood Flow Causes Impaired Fibrinolysis and Endothelial Fibrin Deposition In Vivo

“…Endothelial scratch wound was induced as previously described. 27 Briefly, the carotid artery was dissected free from the surrounding tissue. The ICA was clamped with a micro-vascular clamp and the common carotid artery (CCA) was temporarily ligated by a 6-0 silk ligature snare loop around the mid-portion of the vessel.…”