Coupling of endothelial injury and repair: an analysis using an in vivo experimental model.
The repair of the endothelium after inflammatory injury is essential to maintaining homeostasis. The link between inflammation-induced endothelial damage and repair has not been fully characterized in vivo. We have developed a rat model to evaluate the coupling of lipopolysaccharide (LPS)-induced endothelial injury and repair. Aortic endothelium injury was analyzed by both inmunohistochemistry and flow cytometry to quantify the number of endothelial cells and the percentage of apoptotic endothelial cells. We have also identified the percentage of circulating angiogenic cells capable of repairing the damaged endothelium. Erythropoietin was administered to inhibit LPS-induced endothelial apoptosis. Loss of the normal endothelial structure was observed in the aorta of the animals treated with LPS. Eight hours after LPS administration, the number of endothelial cells decreased by 40%, returning to normal after 24 h. There was a threefold increase in the percentage of circulating angiogenic cells, which did not return to normal levels until 48 h after LPS administration. Circulating angiogenic cell levels did not change when LPS-induced endothelial damage was prevented by erythropoietin. The endothelial injury caused by inflammation activates the mobilization of circulating angiogenic cells, thus completing endothelial repair. Inflammation without endothelial injury does not trigger the mobilization of circulating angiogenic cells.
Nogueras
Sonia
S
Research Unit, Nephrology Service, Reina Sofía University Hospital, ES-14004 Cordova, Spain.
Merino
Ana
A
Ojeda
Raquel
R
Carracedo
Julia
J
Rodriguez
Mariano
M
Martin-Malo
Alejandro
A
Ramírez
Rafael
R
Aljama
Pedro
P
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D001011:Aorta / Q000166:cytology; D017209:Apoptosis / Q000502:physiology; D004730:Endothelium, Vascular / Q000473:pathology*; D004921:Erythropoietin / Q000378:metabolism; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014841:von Willebrand Factor / Q000378:metabolism
D017304:Annexin A5; D008070:Lipopolysaccharides; D014841:von Willebrand Factor; D004921:Erythropoietin