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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2573.)
© 2000 American Heart Association, Inc.

Vascular Biology

Coadministration of Angiopoietin-1 and Vascular Endothelial Growth Factor Enhances Collateral Vascularization

Jei Keon Chae; Injune Kim; Seok Tae Lim; Myoung Ja Chung; Won Ho Kim; Hwan Gyu Kim; Jae Ki Ko; Gou Young Koh

From the National Creative Research Initiatives Center for Cardiac Regeneration and Institute of Cardiovascular Research (J.K.C., I.K., H.G.K, J.K.K., G.Y.K.) and the Departments of Nuclear Medicine (S.T.L), Pathology (M.J.C), and Internal Medicine (W.H.K), Chonbuk University Medical School, Chonju, Korea.

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

Abstract—Using growth factors to induce vasculogenesis is a promising approach in the treatment of ischemic legs and myocardium. Because the vasculogenesis requires a cascade of growth factors, their receptors, and intracellular signals, such therapies may require the application of more than a single growth factor. We examined the effect of 2 endothelial cell–specific growth factors, angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF), on primary cultured porcine coronary artery endothelial cells. VEGF, but not Ang1, increased DNA synthesis and cell number. Ang1 or VEGF induced migration and sprouting activity, increased plasmin and matrix metalloproteinase-2 secretion, and decreased tissue inhibitors of metalloproteinase type 2 secretion. A combination of the submaximal doses of Ang1 and VEGF enhanced these effects and was more potent than the maximal dose of either alone. In a rabbit ischemic hindlimb model, a combination of Ang1 and VEGF gene delivery produced an enhanced effect on resting and maximal blood flow and capillary formation that was greater than that of either factor alone. Angiographic analyses revealed that larger blood vessels were formed after gene delivery of Ang1 or Ang1 plus VEGF than after VEGF gene delivery. These results suggest that combined treatment of Ang1 and VEGF could be used to produce therapeutic vascularization.

Key Words: angiopoietin-1\b • vascular endothelial growth factor\b • vascularization

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