Angiopoietin-like 3 (ANGPTL3) Stimulates Human Umbilical Vein Endothelial Cell Tube Formation and Vascular Endothelial Growth Factor Production

Abstract

Angiogenesis is a physiological process involving the growth of new blood vessels from pre-existing vessels and a fundamental process in the normal development, reproduc- tion, and wound healing. Since angiogenesis in physiological processes is tightly regulated by a balance of stimulatory factors and inhibitory factors, disrupted balance effect plays a leading role in the progress of diseases such as tumor growth, rheumatoid arthritis and various blood vessel related pa- thology. 1-3 Progressive tumor growth is dependent on angio- genesis to receive a supply of oxygen and other essential nutrients. In addition, growth of new vascular capillaries from preexisting vessels provides a way for tumor cells to enter the circulation and to metastasize to distant organs. Among a variety of angiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have a synergistic effect in the induction of angiogenesis. endothelial cells (HUVECs) were treated with CM from control transfected cell and stably transfected cell for 2 h, and HUVECs that had been migrated through membrane pores were counted under microscope. We used VEGF (10 ng/mL) as positive control. CM derived from stably ANGPTL3-trans- fected cells (ANGPTL3-CM) showed significantly induced migratory effect, compared to that of control-CM (Fig. 1A and B). Taken together, these results suggest that ANGPTL3-CM has the biological activity that can induce endothelial cell migration. We next tested the ability of ANGPTL3-CM to promote the mesh-like structures of HUVECs on matrigel. The matrigel angiogenesis assay is generally used for studying HUVEC attachment, migration, and differentiation. The extent of mesh-like structure was more enhanced in HUVECs influenced in ANGPTL3-CM than that of control CM (Fig. 2A and B). Collectively, these data present that ANGPTL3-CM has angio-