fulltext.study @t Gmail

Stimulation of angiogenesis and survival of endothelial cells by human monoclonal Tie2 receptor antibody

Paper ID Volume ID Publish Year Pages File Format Full-Text
5705 417 2015 10 PDF Available
Title
Stimulation of angiogenesis and survival of endothelial cells by human monoclonal Tie2 receptor antibody
Abstract

Angiopoietin-1 (Ang1) and its endothelium-specific receptor, tyrosine kinase with Ig and epidermal growth factor homology domain 2 (Tie2), play critical roles in vascular development. Although the Ang1/Tie2 system has been considered a promising target for therapeutic neovascularization, several imitations of large-scale production have hampered the development of recombinant Ang1 for therapeutics. In this study, we produced a fully human agonistic antibody against Tie2, designated 1–4h, and tested the applicability of 1–4h as an alternative to native Ang1 in therapeutic angiogenesis. 1–4h significantly enhanced the phosphorylation of Tie2 in a dose- and time-dependent manner in human Tie2-expressing HEK293 cells and human umbilical vein endothelial cells. Moreover, 1–4h induced the activation of Tie2-mediated intracellular signaling such as AKT, eNOS, MAPK, and Focal Adhesion Kinase p125FAK. In addition, 1–4h increased the chemotactic motility and capillary-like tube formation of endothelial cells in vitro and enhanced the survival of serum-deprived endothelial cells. Taken together, our data clearly suggest that a human Tie2 agonistic antibody is a potentially useful therapeutic approach for the treatment of several ischemic diseases including delayed-wound healing and ischemic heart and limb diseases.

Keywords
Angiogenesis; Tie2 receptor; Angiopoietin-1; Agonistic antibody
First Page Preview
Stimulation of angiogenesis and survival of endothelial cells by human monoclonal Tie2 receptor antibody
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 51, May 2015, Pages 119–128
Authors
, , , , , , , , , , , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering