This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Coleman, K. R. Articles by Sane, D. C. Search for Related Content PubMed PubMed Citation Articles by Coleman, K. R. Articles by Sane, D. C. Related Collections Animal models of human disease Quantitative modeling Catheter-based coronary interventions: stents Lipid and lipoprotein metabolism

(Circulation Research. 1999;84:1268-1276.)
© 1999 American Heart Association, Inc.

Original Contributions

Vitaxin, a Humanized Monoclonal Antibody to the Vitronectin Receptor (_vß₃), Reduces Neointimal Hyperplasia and Total Vessel Area After Balloon Injury in Hypercholesterolemic Rabbits

Kimberly R. Coleman, Gregory A. Braden, Mark C. Willingham, David C. Sane

From the Section of Cardiology, Department of Internal Medicine (K.R.C., G.A.B., D.C.S.), and Department of Pathology (M.C.W.), Wake Forest University School of Medicine, Winston-Salem, NC.

Correspondence to David C. Sane, Section of Cardiology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1045. E-mail dsane{at}wfubmc.edu

Abstract—The vitronectin receptor (_vß₃) mediates several biological processes that are critical to the formation of a neointima after coronary interventions. Blockade of _vß₃ could reduce neointima formation by inhibiting smooth muscle cell migration, decreasing transforming growth factor-ß₁ expression, enhancing apoptosis, or reducing neovasculature. The effects of short-term administration of Vitaxin, a humanized monoclonal antibody to _vß₃, on the responses to balloon injury were tested in hyperlipidemic rabbits. Balloon angioplasty was performed on the iliac arteries of male New Zealand White rabbits that were fed an atherogenic diet for 1 week before injury and until euthanization at 4 weeks. Rabbits were given either saline (control) or 1 of 2 dosing regimens of Vitaxin (high dose, 5.0 mg/kg, and low dose, 0.5 mg/kg), which were administered intra-arterially before injury and intramuscularly on days 2 and 3. High-dose and low-dose Vitaxin were equally effective in decreasing neointima formation even in the presence of hypercholesterolemia, a stimulus to _vß₃ expression. Vitaxin reduced transforming growth factor-ß₁ and enhanced apoptosis in injured arteries. Despite these positive effects, Vitaxin administration was associated with a reduction in artery size, indicating a negative effect on remodeling. Vitaxin has a potential role in preventing intimal hyperplasia, especially if the negative effects on remodeling can be overcome, by dose adjustment or other strategies.

Key Words: _vß₃ • Vitaxin • balloon angioplasty • hypercholesterolemia • remodeling

This article has been cited by other articles:

				J. L. Wilkinson-Berka, D. Jones, G. Taylor, K. Jaworski, D. J. Kelly, S. B. Ludbrook, R. N. Willette, S. Kumar, and R. E. Gilbert SB-267268, a Nonpeptidic Antagonist of {alpha}v{beta}3 and {alpha}v{beta}5 Integrins, Reduces Angiogenesis and VEGF Expression in a Mouse Model of Retinopathy of Prematurity. Invest. Ophthalmol. Vis. Sci., April 1, 2006; 47(4): 1600 - 1605. [Abstract] [Full Text] [PDF]

				Y. Asano, H. Ihn, K. Yamane, M. Jinnin, Y. Mimura, and K. Tamaki Increased Expression of Integrin {alpha}v{beta}3 Contributes to the Establishment of Autocrine TGF-{beta} Signaling in Scleroderma Fibroblasts J. Immunol., December 1, 2005; 175(11): 7708 - 7718. [Abstract] [Full Text] [PDF]

				Y. Honda, T. Kitano, F. Fukuya, Y. Sato, S. Iwama, T. Morie, and M. Notake A Novel {alpha}v{beta}3 Integrin Antagonist Suppresses Neointima Formation for More Than 4 Weeks After Balloon Injury in Rats Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1376 - 1382. [Abstract] [Full Text] [PDF]

				P. Stawowy, H. Kallisch, J. P. Veinot, A. Kilimnik, W. Prichett, S. Goetze, N. G. Seidah, M. Chretien, E. Fleck, and K. Graf Endoproteolytic Activation of {alpha}v Integrin by Proprotein Convertase PC5 Is Required for Vascular Smooth Muscle Cell Adhesion to Vitronectin and Integrin-Dependent Signaling Circulation, February 17, 2004; 109(6): 770 - 776. [Abstract] [Full Text] [PDF]

				T. Kanzaki and M. Otabe Latent Transforming Growth Factor-{beta} Binding Protein-1, a Component of Latent Transforming Growth Factor-{beta} Complex, Accelerates the Migration of Aortic Smooth Muscle Cells in Diabetic Rats Through Integrin-{beta}3 Diabetes, March 1, 2003; 52(3): 824 - 828. [Abstract] [Full Text] [PDF]

				E. P. Moiseeva Adhesion receptors of vascular smooth muscle cells and their functions Cardiovasc Res, December 1, 2001; 52(3): 372 - 386. [Abstract] [Full Text] [PDF]

				M. Lele, M. Sajid, N. Wajih, and G. A. Stouffer Eptifibatide and 7E3, but Not Tirofiban, Inhibit {alpha}v{beta}3 Integrin-Mediated Binding of Smooth Muscle Cells to Thrombospondin and Prothrombin Circulation, July 31, 2001; 104(5): 582 - 587. [Abstract] [Full Text] [PDF]

				G. G. Bishop, J. A. McPherson, J. M. Sanders, S. E. Hesselbacher, M. J. Feldman, C. A. McNamara, L. W. Gimple, E. R. Powers, S. A. Mousa, and I. J. Sarembock Selective {{alpha}}v{beta}3-Receptor Blockade Reduces Macrophage Infiltration and Restenosis After Balloon Angioplasty in the Atherosclerotic Rabbit Circulation, April 10, 2001; 103(14): 1906 - 1911. [Abstract] [Full Text] [PDF]

				T. J. A. Chico, J. Chamberlain, J. Gunn, N. Arnold, S. L. Bullens, T. R. Gadek, S. E. Francis, S. Bunting, M. Horton, L. Shepherd, et al. Effect of Selective or Combined Inhibition of Integrins {{alpha}}IIb{beta}3 and {{alpha}}v{beta}3 on Thrombosis and Neointima After Oversized Porcine Coronary Angioplasty Circulation, February 27, 2001; 103(8): 1135 - 1141. [Abstract] [Full Text] [PDF]

				M. P. Bendeck, C. Irvin, M. Reidy, L. Smith, D. Mulholland, M. Horton, and C. M. Giachelli Smooth Muscle Cell Matrix Metalloproteinase Production Is Stimulated via {alpha}v{beta}3 Integrin Arterioscler Thromb Vasc Biol, June 1, 2000; 20(6): 1467 - 1472. [Abstract] [Full Text] [PDF]

				S. Kanda, M. Kuzuya, M. A. Ramos, T. Koike, K. Yoshino, S. Ikeda, and A. Iguchi Matrix Metalloproteinase and {alpha}v{beta}3 Integrin-Dependent Vascular Smooth Muscle Cell Invasion Through a Type I Collagen Lattice Arterioscler Thromb Vasc Biol, April 1, 2000; 20(4): 998 - 1005. [Abstract] [Full Text] [PDF]

				D. L. Bhatt, S. P. Marso, A. M. Lincoff, K. E. Wolski, S. G. Ellis, and E. J. Topol Abciximab reduces mortality in diabetics following percutaneous coronary intervention J. Am. Coll. Cardiol., March 15, 2000; 35(4): 922 - 928. [Abstract] [Full Text] [PDF]

				G. Pasterkamp, D. P.V de Kleijn, and C. Borst Arterial remodeling in atherosclerosis, restenosis and after alteration of blood flow: potential mechanisms and clinical implications Cardiovasc Res, March 1, 2000; 45(4): 843 - 852. [Abstract] [Full Text] [PDF]

				M. Rezaee, K. Penta, and T. Quertermous Del1 mediates VSMC adhesion, migration, and proliferation through interaction with integrin alpha vbeta 3 Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1924 - H1932. [Abstract] [Full Text] [PDF]