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See article by Kim et al. [6] (pages 394−402) in this issue. The Tie2/angiopoietin pathway is crucial for angiogenesis, blood vessel maturation, and vascular endothelial integrity. The ligands for Tie2 are the angiopoietins, of which angiopoietin-1 (Ang1) and Ang2 have been the most studied. Suppression of plasma leakage, inhibition of vascular inflammation, and prevention of endothelial death are the three widely accepted vascular protective functions for Ang1 [1], the first ligand identified for the Tie2 receptor. However, the role of Ang2, a relative of Ang1 identified by homology screening, remains less clear, because Ang2 exhibits context-dependent behavior. Ang2 can inhibit or stimulate Tie2 receptor phosphorylation under different experimental conditions [2]. Ang2 in vivo acts as a Tie2 antagonist on vascular endothelial cells (ECs), whereas it acts as a Tie2 agonist on lymphatic vessels [3]. Recently, increased Ang2 expression was demonstrated in myocardial ischemia and infarction [4,5], indicating the role of Ang2 in the angiogenic response to tissue ischemia.In this issue of Cardiovascular Research , Kim et al. [6] report a proangiogenic activity of Ang2 in endothelial progenitor cells (EPCs) directly through the Tie2 signaling pathway. Ang2 increased tube formation, migration, and cell survival of EPCs derived from human umbilical cord … *Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. Tel.: +886 2 2833 2211; fax: +886 2 2836 5775. Email address: shyukg{at}ms12.hinet.net

Enhancement of new vessel formation by Angiopoietin-2/Tie2 signaling in endothelial progenitor cells: A new hope for future therapy?