Cardiovascular Gene Therapy
We are poised on the threshold of a new era; the ability to alter the genetic make up and/or expression of genes in humans. The prospect is a single injection of a gene therapeutic curing familial hypercholesterolemia, correcting severe combined immunodeficiency, removing the death sentence from those with a hereditary colon cancer gene, or growing new blood vessels to relieve chronic myocardial ischemia. The last decade has seen much progress toward reaching these goals, but we are not there yet. We review here the status of cardiovascular gene therapy in the published literature as of February 1998; mindful of the rapidly moving field we are surveying.
KeywordsPlacebo Cholesterol Toxicity Ischemia Lipase
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- Aoki M, Morishita R, Muraishi A, Moriguchi A, Sugimoto T, Maeda K, Dzau VJ, Kaneda Y, Higaki J, Ogihara T (1997) Efficient in vivo gene transfer into the heart in the rat myocardial infarction model using the HVJ (hemag-glutinating virus of Japan)-liposome method. J Mol Cell Cardiol 29:949–959PubMedCrossRefGoogle Scholar
- Giordano FJ, Ping P, McKirnan MD, Nozaki S, DeMaria AN, Dillmann WH, Mathieu-Costello O, Hammond HK (1996) Intracoronary gene transfer of fibroblast growth factor-5 increases blood flow and contractile function in an ischemic region of the heart (see comments). Nat Med 2:534–539PubMedCrossRefGoogle Scholar
- Guzman RJ, Hirschowitz EA, Brody SL, Crystal RG, Epstein SE, Finkel T (1994) In vivo suppression of injury-induced vascular smooth muscle cell accumulation using adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene. Proc Natl Acad Sci USA 91:10732–10736PubMedCrossRefGoogle Scholar
- Lazarous DF, Shou M, Scheinowitz M, Hodge E, Thirumurti V, Kitsiou AN, Stiber JA, Lobo AD, Hunsberger S, Guetta E, Epstein SE, Unger EF (1996) Comparative effects of basic fibroblast growth factor and vascular endothelial growth factor on coronary collateral development and the arterial response to injury. Circulation 94:1074–1082PubMedCrossRefGoogle Scholar
- Li J, Fang B, Eisensmith RC, Li XH, Nasonkin I, Lin-Lee YC, Mims MP, Hughes A, Montgomery CD, Roberts JD (1995) In vivo gene therapy for hyperlipidemia: phenotypic correction in Watanabe rabbits by hepatic delivery of the rabbit LDL receptor gene. J Clin Invest 95:768–773PubMedCrossRefGoogle Scholar
- Mack CA, Patel SR, Schwarz EA, Zanzonico P, Hahn RT, Ilercil A, Devereux RB, Goldsmith SJ, Christian TF, Sanborn TA, Kovesdi I, Hackett N, Isom OW, Crystal RG, Rosengart TK (1998) Biologic bypass with the use of ade-novirus-mediated gene transfer of the complementary deoxyribonucleic acid for vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart. J Thorac Cardiovasc Surg 115:168–176; discussion 176–177PubMedCrossRefGoogle Scholar
- Schulick AH, Vassalli G, Dunn PF, Dong G, Rade JJ, Zamarron C, Dichek DA (1997) Established immunity precludes adenovirus-mediated gene transfer in rat carotid arteries. Potential for immunosuppression and vector engineering to overcome barriers of immunity. J Clin Invest 99:209–219PubMedCrossRefGoogle Scholar
- Takeshita S, Weir L, Chen D, Zheng LP, Riessen R, Bauters C, Symes JF, Ferrara N, Isner JM (1996) Therapeutic angiogenesis following arterial gene transfer of vascular endothelial growth factor in a rabbit model of hindlimb ischemia. Biochem Biophys Res Commun 227:628–635PubMedCrossRefGoogle Scholar
- Tsunami Y, Takeshita S, Chen D, Kearney M, Rossow ST, Passeri J, Horowitz JR, Symes JF, Isner JM (1996) Direct intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor augments collateral development and tissue perfusion (see comments). Circulation 94:3281–3290CrossRefGoogle Scholar