Resident endothelial cells surrounding damaged arterial endothelium reendothelialize the lesion

Objective: To evaluate endothelial repair processes in denuded pial vessels to clarify mechanisms for reconstructing endothelium (because endothelial repair of the cerebral artery after its damage is critical for the prevention of thrombosis, the maintenance of vascular tone, and the protection of the brain by the blood-brain barrier). Methods and Results: Endothelial cells (ECs) in a 350-μm-long segment of the middle cerebral artery were damaged through a photochemical reaction. Tie2-green fluorescent protein transgenic mice were used for the identification of ECs. Six hours after the endothelial damage, ECs were detached from the luminal surface of the damaged artery, which was then covered with a platelet carpet. Within 24 hours, recovery of the denuded artery started at both edges, with EC elongation and migration. The repair rate was faster at the proximal edge than at the distal edge. Reendothelialization with EC proliferation peaked at 2 to 3 days and ended at 5 days, together with normalization of EC length, with no apparent involvement of foreign progenitor cells. Conclusion: Our in vivo study demonstrated a stepwise reendothelialization process by resident ECs of the pial artery. The prevention of thrombosis, vasospasm, and treatment for blood-brain barrier dysfunction should be considered during the reendothelialization period.