This Article Full Text (PDF) References 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 Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Chandiwal, A. Articles by Schwartz, L. B. Search for Related Content PubMed PubMed Citation Articles by Chandiwal, A. Articles by Schwartz, L. B. Social Bookmarking                         What's this?

Gene Therapy for the Extension of Vein Graft Patency: A Review

Section of Vascular Surgery, Department of Surgery; University of Chicago; Boston, MA

Viji Balasubramanian, PhD

Section of Vascular Surgery, Department of Surgery; University of Chicago; Department of Biomedical Engineering; Illinois Institute of Technology, Chicago; Boston, MA

Zachary K. Baldwin, MD

Section of Vascular Surgery, Department of Surgery; University of Chicago; Boston, MA

Michael S. Conte, MD

Division of Vascular Surgery; Brigham and Women's Hospital, Boston, MA; Chicago, IL

Lewis B. Schwartz, MD

Section of Vascular Surgery, Department of Surgery; University of Chicago; Boston, MA

The mainstay of treatment for long-segment small-vessel chronic occlusive disease not amenable to endovascular intervention remains surgical bypass grafting using autologous vein. The procedure is largely successful and the immediate operative results almost always favorable. However, the lifespan of a given vein graft is highly variable, and less than 50% will remain primarily patent after 5 years. The slow process of graft malfunction is a result of the vein's chronic maladaptive response to the systemic arterial environment, its primary component being the uncontrolled proliferation of vascular smooth muscle cells (SMCs). It has recently been suggested that this response might be attenuated through pre-implantation genetic modification of the vein, so-called gene therapy for the extension of vein graft patency. Gene therapy seems particularly well suited for the prevention or postponement of vein graft failure since: (1) the stimulation of SMC proliferation appears to largely be an early and transient process, matching the kinetics of current gene transfer technology; (2) most veins are relatively normal and free of disease at the time of bypass allowing for effective gene transfer using a variety of systems; and (3) the target tissue is directly accessible during operation because manipulation and irrigation of the vein is part of the normal workflow of the surgical procedure. This review briefly summarizes the current knowledge of the incidence and basic mechanisms of vein graft failure, the vector systems and molecular targets that have been proposed as possible pre-treatments, the results of experimental genetic modification of vein grafts, and the few available clinical studies of gene therapy for vascular proliferative disorders.

Vascular and Endovascular Surgery, Vol. 39, No. 1, 1-14 (2005)
DOI: 10.1177/153857440503900101


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?