Abstract
The human body contains different endothelial cell types and differences in their angiogenic potential are poorly understood. We compared the functional angiogenic ability of human aortic endothelial cells (HAECs) and human umbilical vein endothelial cells (HUVECs) using a three-dimensional (3D) microfluidic cell culture system. HAECs and HUVECs exhibited similar cellular characteristics in a 2D culture system; however, in the 3D microfluidic angiogenesis system, HAECs exhibited stronger angiogenic potential than HUVECs. Interestingly, the expression level of fibroblast growth factor (FGF)2 and FGF5 under vascular endothelial growth factor (VEGF)-A stimulation was significantly higher in HAECs than in HUVECs. Moreover, small interfering RNA-mediated knockdown of FGF2 and FGF5 more significantly attenuated vascular sprouting induced from HAECs than HUVECs. Our results suggest that HAECs have greater angiogenic potential through FGF2 and FGF5 upregulation and could be a compatible endothelial cell type to achieve robust angiogenesis.
Highlights
Vessels[18,19]
The study presents that; (i) human aortic endothelial cells (HAECs) show higher angiogenic potential than human umbilical vein endothelial cells (HUVECs) under VEGF-A stimulation only in 3D microfluidic angiogenesis system, and (ii) endogenous FGF2 and FGF5 expression in both cell types is a crucial regulator of angiogenesis, increased expression of FGF5 rather than that of FGF2 extends greater angiogenic potential to HAECs
The 3D microfluidic angiogenesis system used in the study is found to be powerful for understanding stereoscopic cellular morphogenesis of 3D cooperative migration and morphogenesis of endothelial cells[31,32]
Summary
FGF5 is well known to have tight connection with hair growth cycle[20], and gene transfer of FGF5 into injured myocardium was reported to promote blood flow and enhanced vessel formation[21,22]. Role of FGF5 for angiogenesis has not been known much. The role of FGF ligands and receptors in different endothelial cell types is poorly understood. Three-dimensional (3D) microfluidic angiogenesis systems have been adopted in vascular research[23,24,25] They can form 3D tube-like angiogenic structures, perfectly circular and randomly distributed in 3D extracellular matrix (ECM) scaffold. The features of the 3D microfluidic angiogenesis system were successfully adopted by in vivo mimicking of vascular sprouting via a VEGF-A gradient[29] and a precise computational simulation[25] to a detailed comparison of the angiogenic potential of HAECs and HUVECs
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