OVEREXPRESSION OF MIRNA-146A PROMOTING THE PROLIFERATION AND ANGIOGENESIS OF HUMAN CORONARY ARTERY ENDOTHELIAL CELLS VIA NF2

HAI-TAO HUANG#, FEI WANG#, SHENG-GUANG DING#, YONG-BO TIAN#,YI-MING XU, CHONG-JUN ZHONG*

Department of Thoracic and Cardiovascular Surgery, Nantong First People’s Hospital, Nantong 226001, Jiangsu Province, China

Background: MicroRNA-146a (miR-146a) is reportedly implicated in the pathogenesis of cancer cells. Its role in the human coronary artery endothelial cells (HCAECs) is however unclear. In this study, the effects of miR-146a on the proliferation and angio- genesis of HCAECs were investigated.

Methods: MiR-146a was up- or down-regulated by transfection of mimic or inhibitor. BrdU assay was used to evaluate the proliferation of HCAECs. Wound healing assay and Transwell penetrating experiment were performed to investigate the migration and penetrating ability. We investigated whether miR-146a influences the secretion of vascular endothelial growth factor (VEGF) and angiogenesis of HCAECs. Regulatory mechanism of miR-146a was investigated meanwhile.

Results: MiR-146a mimic promote the proliferation, migration, penetrating, angiogenesis ability of HCAECs. Overexpression of miR-146a decreased the expression of neurofibromin 2, but increased the expression of PAK1 and VEGF followed with the enhancement of angiogenesis. The up-regulation effect of VEGF by miR-146a can be blocked by overexpression of NF2 .

Conclusions: MiR-146a can increase the proliferation, migration and penetrating ability of HCAECs, and promote angiogene- sis by up-regulating expression of VEGF via NF2/PAK1 pathway. Upregulation of miR-146a may be a new therapeutic target to improve the blood supply for acute myocardial infarction.