Objective This study was aimed to investigate the effects of carbon monoxide releasing molecule(CORM-2), a novel carbon monoxide carrier, on the reendothelialization of carotid artery in rat endothelial denudation model. Methods Male rats subjected to carotid artery balloon injury were treated with CORM-2, inactive CORM-2(i CORM-2) or dimethyl sulfoxide(DMSO). The reendothelialization capacity was evaluated by Evans Blue dye and the immunostaining with anti-CD31 antibody. The number of circulating endothelial progenitor cells(EPCs) was detected by flow cytometry. The proliferation, migration, and adhesion of human umbilical vein endothelial cells(HUVECs) were assessed by using [3H]thymidine, Boyden chamber and human fibronectin respectively. The expressions of protein were detected by using western blot analysis. Results CORM-2 remarkably accelerated the re-endothelialization 5 d later and inhibited neointima formation 28 d later. In addition, the number of peripheral EPCs significantly increased in CORM-2-treated rats than that in i CORM-2 or DMSO-treated rats after 5 d later. In vitro experiments, CORM-2 significantly enhanced the proliferation, migration and adhesion of HUVECs. The levels of Akt, e NOS phosphorylation, and NO generation in HUVECs were also much higher in CORM-2 treated group. Blocking of PI3K/Akt/e NOS signaling pathway markedly suppressed the enhanced migration and adhesion of HUVECs induced by CORM-2. Conclusion CORM-2 could promote endothelial repair, and inhibit neointima formation after carotid artery balloon injury, which might be associated with the function changes of HUVECs regulated by PI3K/Akt/e NOS pathway.
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