PMID- 23125915 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20121106 LR - 20211021 IS - 2090-0015 (Electronic) IS - 2090-0007 (Print) IS - 2090-0007 (Linking) VI - 2012 DP - 2012 TI - Gene transfer of heme oxygenase-1 using an adeno-associated virus serotype 6 vector prolongs cardiac allograft survival. PG - 740653 LID - 10.1155/2012/740653 [doi] LID - 740653 AB - 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 or partially mismatched at the MHC, was determined with and without cyclosporine A. Intragraft cytokine gene expression was examined by PCR. Results. The use of AAV6 to deliver HO-1 to the donor heart, combined with immunosuppression, prolonged allograft survival by 55.3% when donor and recipient were completely mismatched at the MHC and by 94.6% if partially mismatched. The combination of gene therapy and immunosuppression was more beneficial than treatment with either AAV6-HO-1 or CsA alone. IL-17a, b, e and f were induced in the heart at rejection. Conclusions. Pretreatment of cardiac allografts with AAV6-HO-1 plus cyclosporine A prolonged graft survival. HO-1 gene therapy represents a beneficial adjunct to immunosuppressive therapy in cardiac transplantation. FAU - Evans, Jacqueline M AU - Evans JM AD - Department of Anesthesiology Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA. FAU - Navarro, Sonia AU - Navarro S FAU - Doki, Tomoko AU - Doki T FAU - Stewart, John M AU - Stewart JM FAU - Mitsuhashi, Noboru AU - Mitsuhashi N FAU - Kearns-Jonker, Mary AU - Kearns-Jonker M LA - eng PT - Journal Article DEP - 20121016 PL - United States TA - J Transplant JT - Journal of transplantation JID - 101519118 PMC - PMC3480008 EDAT- 2012/11/06 06:00 MHDA- 2012/11/06 06:01 PMCR- 2012/10/16 CRDT- 2012/11/06 06:00 PHST- 2012/05/18 00:00 [received] PHST- 2012/09/07 00:00 [revised] PHST- 2012/09/07 00:00 [accepted] PHST- 2012/11/06 06:00 [entrez] PHST- 2012/11/06 06:00 [pubmed] PHST- 2012/11/06 06:01 [medline] PHST- 2012/10/16 00:00 [pmc-release] AID - 10.1155/2012/740653 [doi] PST - ppublish SO - J Transplant. 2012;2012:740653. doi: 10.1155/2012/740653. Epub 2012 Oct 16.