gene transfer of heme oxygenase-1 using an adeno-associated virus serotype 6 vector prolongs cardiac allograft survival基因转移的血红素oxygenase-1使用腺相关病毒血清型6向量延长移植物存活.pdfVIP

Hindawi Publishing Corporation Journal of Transplantation Volume 2012, Article ID 740653, 10 pages doi:10.1155/2012/740653 Research Article Gene Transfer of Heme Oxygenase-1 Using an Adeno-Associated Virus Serotype 6 Vector Prolongs Cardiac Allograft Survival Jacqueline M. Evans,1 Sonia Navarro,1 Tomoko Doki,2 John M. Stewart,3 Noboru Mitsuhashi,2 and Mary Kearns-Jonker2, 3 1 Department of Anesthesiology Critical Care Medicine, Children’s Hospital Los Angeles, Los Angeles, CA 90027, USA 2 Department of Cardiothoracic Surgery, Children’s Hospital Los Angeles, Los Angeles, CA 90027, USA 3 Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Alumni Hall Room 326, 11021 Campus Street, Loma Linda, CA 92350, USA Correspondence should be addressed to Mary Kearns-Jonker, mkearnsjonker@ Received 18 May 2012; Revised 7 September 2012; Accepted 7 September 2012 Academic Editor: Simon Robson Copyright © 2012 Jacqueline M. Evans et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Introduction. Allograft survival can be prolonged by overexpression of cytoprotective genes such as heme oxygenase-1 (HO-1). Modifications in vector design and delivery have provided new opportunities to safely and effectively administer HO-1 into the heart prior to transplantation to improve long-term graft outcome. Methods. HO-1 was delivered to the donor heart using an adeno-associated virus vector (AAV) with a pseudotype 6 capsid and vascular endothelial growth factor (VEGF) to enhance myocardial tropism and microvascular permeability. Survival of mouse cardiac allografts, fully