Endothelial progenitor cells overexpressed with omentin-1 enhance the inhibition of neointimal hyperplasia via anti-inflammation

Abstract Background Endothelial progenitor cells (EPCs) play an important role in vascular repair. However, the functions of EPCs are obviously weakened in inflammatory microenvironment during restenosis. Therefore, we investigated whether omentin-1, an anti-inflammatory factor, can reduce neointima formation after carotid artery injury (CAI) in rats via improving EPCs functions damaged by inflammation and the underlying mechanisms. Methods Rats bone marrow-derived EPCs were isolated and cultured. EPCs were transfected with adenovirus vectors expressing human omentin-1 or green fluorescent protein (GFP). Rats received 2×106 EPCs with expressing omentin-1 or GFP by tail vein injection directly after CAI and again 24 h later. Hematoxylin-eosin staining and immunohistochemistry were used for analyzing neointimal hyperplasia. Besides, EPCs were treated with omentin-1 and tumor necrosis factor-α (TNF-α) in order to explore the underlying mechanism. Results Omentin-1 could significantly promote EPCs proliferation and tube formation, as well as inhibit apoptosis. EPCs overexpressed with omentin-1 using adenovirus vectors could extremely reduce the neointimal hyperplasia after CAI in rats. Besides, TNF-α could notably induce EPCs dysfunction including reduced proliferation, migration tube formation and increased apoptosis, which can be remarkably attenuated by omentin-1 via inhibiting of p38/CREB pathway. Besides, p38 agonist (anisomycin) could significantly reverse the protective effects of omentin-1 which attenuated the injury effects of TNF-α on EPCs. Conclusions EPCs overexpressed with omentin-1 can significantly reduce neointima formation after arterial injury by enhancing the functions of EPCs via inhibiting the p38/CREB pathway. Our results indicate that gene modified EPCs with omentin-1 may be an alternative strategy for the treatment of restenosis.