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Circulation Research. 2000;86:952-959

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(Circulation Research. 2000;86:952.)
© 2000 American Heart Association, Inc.


Cellular Biology

Angiopoietin-1 Induces Endothelial Cell Sprouting Through the Activation of Focal Adhesion Kinase and Plasmin Secretion

Injune Kim, Hwan Gyu Kim, Sang-Ok Moon, Soo Wan Chae, June-No So, Keum Nim Koh, Byung Cook Ahn, Gou Young Koh

From the National Creative Research Initiatives Center for Cardiac Regeneration and Institute of Cardiovascular Research (I.K., H.G.K., S.-O.M., S.W.C., J.-N.S., K.N.K., G.Y.K.) and Department of Ophthalmology (B.C.A.), Chonbuk National University School of Medicine, and Department of Biotechnology (J.-N.S.), Woosuk University, Chonju, Korea.

Correspondence to Gou Young Koh, MD, PhD, National Creative Research Initiatives Center for Cardiac Regeneration, Chonbuk National University School of Medicine, San 2-20, Keum-Am-Dong, Chonju, 560-180, Republic of Korea. E-mail gykoh{at}moak.chonbuk.ac.kr

Abstract—Angiopoietin-1 (Ang1) is a strong inducer of endothelial cell sprouting, which is a first step in both angiogenesis and neovascularization. We examined the mechanisms underlying Ang1-induced cell sprouting using porcine pulmonary artery endothelial cells. Ang1 induced the nondirectional and directional migration of endothelial cells mediated through the Tie2 but not the Tie1 receptor. Ang1 induced tyrosine phosphorylation of p125FAK, and this phosphorylation was dependent on phosphatidylinositol (PI) 3'-kinase activity. Ang1 induced the secretion of plasmin and matrix metalloproteinase-2 (MMP-2), which is inhibited by PI 3'-kinase inhibitors. Ang1 also induced the secretion of small amounts of proMMP-3 and proMMP-9 but not proMMP-1. Ang1 suppressed the secretion of tissue inhibitor of metalloproteinase-2 (TIMP-2), but not of TIMP-1. Addition of {alpha}2-antiplasmin, a combination of TIMP-1 and TIMP-2, or PI 3'-kinase inhibitors inhibited Ang1-induced sprouting activity. Therefore, Ang1-induced sprouting activity in endothelial cells may be accomplished by cytoskeletal changes and secretion of proteinases and may be largely mediated through intracellular PI 3'-kinase activation.


Key Words: angiopoietin-1 • sprouting • p125FAK • plasmin




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