Overexpression of Angiopoietin-1 Potentiates Endothelial Progenitor Cells for the Treatment of Aneurysm.

BACKGROUND:To investigate whether angiopoietin-1 (Ang-1) could regulate the endothelial progenitor cells (EPCs) survival and the effect of accelerating intra-aneurysmal organization and occlusion of the aneurysm neck. METHODS:EPCs were isolated from Wistar rats. EPCs were cultured and transfected with lentivirus-Ang-1-endothelial progenitor cells (Ang-1-EPCs) and lentivirus-NC-endothelial progenitor cells (NC-EPCs). The effects of Ang-1 on viability and functioning of EPCs were explored via tube formation, migration, and MTT (3-[4,5-dimethylthiazolyl-2]-2,5-diphenyltetrazolium bromide) assays. Eighteen Wistar rats were randomly allocated into 3 groups. Eighteen bare coils were inserted into the ligated external carotid artery (ECA) sacs of rats. The ECA sacs were removed 2 weeks after the coils were implanted and examined by histology assay. RESULTS:Ang-1 significantly promoted EPCs tube formation, migration, and proliferation ability in vitro. Histology analyses revealed that the organized areas in the ECA sacs in the Ang-1-EPCs group are higher than NC-EPCs group and control group at 2 weeks. Immunofluorescence revealed that organized tissues were characterized by an accumulation of cells positive for α-smooth muscle actin-positive cells in aneurysm sacs. CONCLUSIONS:Overexpression of Ang-1 enhanced the tube formation, migration, and proliferation ability of EPCs. Ang-1 gene-modified EPCs accelerated organization within the aneurysms and occlusion of aneurysm neck. Transplantation of Ang-1-transfected EPCs may be a new method for the treatment of aneurysm.

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