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(Circulation. 1996;94:1074-1082.)
© 1996 American Heart Association, Inc.

Articles

Comparative Effects of Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor on Coronary Collateral Development and the Arterial Response to Injury

Daisy F. Lazarous, MD; Matie Shou, MD; Mickey Scheinowitz, PhD; Everett Hodge; Venugopal Thirumurti, MD; Anastasia N. Kitsiou, MD; Jonathan A. Stiber, BS; Arlene D. Lobo, BS; Sally Hunsberger, PhD; Esther Guetta, PhD; Stephen E. Epstein, MD; Ellis F. Unger, MD

the Experimental Physiology and Pharmacology Section, Cardiology Branch (D.F.L., M. Shou, M. Scheinowitz, E.H., V.T., A.N.K., J.A.S., A.D.L., E.G., S.E.E., E.F.U.), and the Biostatistics Research Branch (S.H.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.

Correspondence to Daisy F. Lazarous, MD, Cardiology Branch, NHLBI, NIH, Bldg 10, Room 7B15, 10 Center Dr, MSC 1650, Bethesda, MD 20892-1650.

Background We have shown that the angiogenic peptides basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) enhance canine coronary collateral development when administered for 4 weeks. bFGF, a pluripotent mitogen of mesodermally derived cells, could theoretically exacerbate neointimal smooth muscle cell hyperplasia, a fundamental component of atherosclerosis. VEGF, an endothelial cell–specific mitogen and vascular permeability factor, could have deleterious effects related to vascular hyperpermeability. The present investigation had two aims: (1) to ascertain whether brief (7-day) systemic arterial treatment with bFGF or VEGF would improve myocardial collateral perfusion and (2) to determine whether these peptides induce neointimal accumulation in vivo.

Methods and Results Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery and randomized to bFGF 1.74 mg (n=9), VEGF 0.72 mg (n=9), or saline (n=10) as a daily left atrial bolus (days 10 to 16). Additional dogs were randomized to VEGF 0.72 mg (n=6) or saline (n=5); however, treatment was delayed by 1 week. Coincident with the institution of treatment, all dogs underwent balloon denudation injury of the iliofemoral artery. bFGF markedly increased maximal collateral flow but did not exacerbate neointimal accumulation. VEGF had no discernible effect on maximal collateral flow, but it exacerbated neointimal thickening after vascular injury.

Conclusions Short-term treatment with bFGF enhanced collateral development without increasing neointimal accumulation at sites of vascular injury. Although VEGF did not increase collateral development as administered in this study, it significantly exacerbated neointimal accumulation. These data provide support for the clinical investigation of bFGF in selected patients with ischemic heart disease.

Key Words: angiogenesis • collateral circulation • muscle, smooth • growth substances

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