Study On The Relationship Between Fibulin-3 And Vascular Endothelial Dysfunction And Angiotensin Ⅱ In Hypertension

Vascular endothelial dysfunction is the important pathogenesis of hypertension.In this study,we investigated the relationship between Fibulin-3 and vascular endothelial injury and Angiotensin II(AngII)in essential hypertension via the in vivo and in vitro experiments.108 patients with essential hypertension(EH group)and 31 healthy peoples(control group)were included to measure the folw-mediated dilatation(FMD)by the vascular endothelial function detector.The serum Fibulin-3and AngII were examed by enzyme-linked immunosorbent assay and radio immunoassay,respectively.Stable transfection of Fibulin-3 was conducted to knockdown and overexpress Fibulin-3 in human umbilical vein endothelial cells(HUVECs)and AngII was added to HUVECs,to explore the effect of Fibulin-3 and AngII on endothelial cell function.Cell migration,proliferation,apoptosis and angiogenesis were examined using wound healing assay,Transwell assay,Cell Counting Kit‐8(CCK-8),cell cycle assay,apoptosis assay and tube formation assay,respectively.HUVECs were treated with AngII and with the selective inhibitor(BAY11-7082)of the nuclear factor kappa B(NF-κ B)pathway or not,to explore the effect and the underlying mechanism of AngII on Fibulin-3 in endothelial cells.Firstly,our results elucidated that the EH group had significantly lower levels of serum Fibulin-3 and FMD,but had significantly higher levels of serum AngII.What is more,Fibulin-3 was positively correlated with FMD and negatively correlated with AngII in essential hypertension patients.Secondly,stable knockdown of Fibulin-3suppressed HUVECs migration,proliferation,angiogenesis and enhanced apoptosis,whereas elevated levels of Fibulin-3 promoted migration,proliferation,angiogenesis but inhibited apoptosis of HUVECs.Thirdly,AngII enhanced the migration and proliferation of HUVECs,but promoted the apoptosis of HUVECs,and inhibited the angiogenesis of HUVECs.Fourthly,the selective inhibitor of NF-κB(BAY 11-7082)could eliminate the inhibition effect of AngII on Fibulin-3 expression in HUVECs.In summary,serum Fibulin-3 was positively correlated with FMD in patients with hypertension,but negatively correlated with serum AngII,suggesting that serum Fibulin-3 could be used as a predictor of vascular endothelial injury in patients with hypertension.Downregulation of Fibulin-3expression inhibited the migration,proliferation and angiogenesis of vascular endothelial cells.Overexpression of Fibulin-3 promoted the migration,proliferation and angiogenesis of vascular endothelial cells.Fibulin-3 may be a repair factor for vascular endothelial in hypertension.AngII inhibited the function of vascular endothelial cells and the expression of Fibulin-3 in endothelial cells through NF-κ B signaling pathway.Fibulin-3 played an important role in maintaining the physiological function of vascular endothelium.