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Vascular Cell Proliferation Dynamics: Implications for Gene Transfer and Restenosis

  • Chapter
Gene Transfer in the Cardiovascular System

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 189))

Abstract

Pharmacologic treatment of restenosis following coronary angioplasty has completely failed. The most widely accepted cause is formation of neointimal hyperplasia, considered a result of uncontrolled medial smooth muscle cell proliferation [1–5]. Studies in the rat carotid artery injury model has been the basis of this paradigm, having been documented in many studies [6, 7]. Therapies aimed at inhibiting proliferation have been quite successful in rat arterial injury [8, 9]. Yet when applied to large scale patient trials, these therapies have failed to exhibit any effect whatsoever on the loss of minimal lumen diameter (MLD) [10]. Reasons for these failures are unclear, but may relate in part to an incomplete understanding of cell kinetics in the growth of human neointimal hyperplasia. The literature is conflicting regarding the role of proliferation in human restenosis. Two studies of human restenotic lesions obtained using directional atherectomy demonstrated opposite conclusions. Pickering and colleagues [11] found peak cellular proliferation rates of about 20%, while in a similar study, O’Brien [12] reported a proliferation rate of less than 1%. Much debate has surfaced about the reasons for these divergent results, but centers on questions of technical factors such as tissue fixation methods and visual interpretation of positive cells by proliferating cell nuclear antigen (PCNA) staining.

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Authors and Affiliations

  1. Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Foundation, Rochester, MN, USA

    Robert S. Schwartz MD, FACC, Aloysius Chu MS, Myung Ho Jeong MD, Michael E. Staab MD, Sanjay S. Srivatsa MBBChir, Vincent J. Pompili MD & David R. Holmes Jr. MD, FACC

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  1. Robert S. Schwartz MD, FACC
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  2. Aloysius Chu MS
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  3. Myung Ho Jeong MD
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  4. Michael E. Staab MD
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  5. Sanjay S. Srivatsa MBBChir
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  6. Vincent J. Pompili MD
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  7. David R. Holmes Jr. MD, FACC
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Editor information

Editors and Affiliations

  1. Krannert Institute of Cardiology, Indiana University Medical Center, Indianapolis, Indiana, USA

    Keith L. March M.D., Ph.D.

  2. R. L. Roudebush VA Medical Center, Indianapolis, Indiana, USA

    Keith L. March M.D., Ph.D.

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© 1997 Springer Science+Business Media New York

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Schwartz, R.S. et al. (1997). Vascular Cell Proliferation Dynamics: Implications for Gene Transfer and Restenosis. In: March, K.L. (eds) Gene Transfer in the Cardiovascular System. Developments in Cardiovascular Medicine, vol 189. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-6277-1_13

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  • DOI: https://doi.org/10.1007/978-1-4615-6277-1_13

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7881-5

  • Online ISBN: 978-1-4615-6277-1

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