Abstract
Adenovirus-mediated gene transfer is a promising method for studies of vascular biology and potentially for gene therapy. Intravascular approaches for gene transfer to blood vessels in vivo generally require interruption of blood flow and have several limitations. We have used two alternative approaches for gene transfer to blood vessels in vivo using perivascular application of vectors. First, replication-deficient adenovirus expressing nuclear-targeted bacterial β-galactosidase was injected into cerebrospinal fluid via the cisterna magna of rats. Leptomeningeal cells over the major arteries were efficiently transfected, and adventitial cells of large vessels and smooth muscle cells of small vessels were occasionally stained. When viral suspension was injected with the rat in a lateral position, the reporter gene was expressed extensively on the ipsilateral surface of the brain. Thus, adenovirus injected into cerebrospinal fluid provides gene transfer in vivo to cerebral blood vessels and, with greater efficiency, to perivascular tissue. Furthermore, positioning of the head may ‘target’ specific regions of the brain. Second, vascular gene delivery was accomplished by perivascular injection of virus in peripheral vessels. Injection of the adenoviral vector within the periarterial sheath of monkeys resulted in gene transfer to the vessel wall that was substantial in magnitude although limited to cells in the adventitia. Approximately 20% of adventitial cells expressed the transgene, with no gene transfer to cells in the intima or media. These approaches may provide alternative approaches for gene transfer to blood vessels, and may be useful for studies of vascular biology and perhaps vascular gene therapy. (Mol Cell Biochem 172: 37–46, 1997)
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References
Nabel EG, Plautz G, Nabel GJ: Site-specific gene expression in vivo by direct gene transfer into the arterial wall. Science 249: 1285–1288, 1990
Lim CS, Chapman GD, Gammon RS, Mublestein JB, Bauman RP, Stack RS, Swain JL: Direct in vivo gene transfer into the coronary and peripheral vasculatures of the intact dog. Circulation 83: 2007–2011, 1991
Chapman GD, Lim CS, Gammon RS, Culp SC, Desper JS, Bauman RP, Swain JL, Stack RS: Gene transfer into coronary arteries of intact animals with a percutaneous balloon catheter. Circ Res 71: 27–33, 1992
Nabel EG, Plautz G, Nabel GJ: Transduction of a foreign histocompatibility gene into the arterial wall induces vasculitis. Proc Natl Sci USA 89: 5157–5161, 1992
Leclerc G, Gal D, Takeshita S, Nikol S, Weir L, Isner JM: Percutaneous arterial gene transfer in a rabbit model. Efficiency in normal and balloon-dilated atherosclerotic arteries. J Clin Invest 90: 936–944, 1992
Nabel EG, Yang Z, Liptay S, San H, Gordon D, Haudenschild CC, Nabel GJ: Recombinant platelet-derived growth factor B gene expression in porcine arteries induces intimal hyperplasia in vivo. J Clin Invest 91: 1822–1829, 1993
Nabel EG, Shum L, Pompili VJ, Yang Z-Y, San H, Shu HB, Liptay S, Gold L, Gordon D, Derynck R, Nabel GJ: Direct transfer of transforming growth factor β1 gene into arteries stimulates fibrocellular hyperplasia. Proc Natl Acad Sci USA 90: 10759–10763, 1993
Takeshita S, Gal D, Leclerc G, Pickering JG, Riessen R, Weir L, Isner JM: Increased gene expression after liposome-mediated arterial gene transfer associated with intimal smooth muscle cell proliferation. In vitro and in vivo findings in a rabbit model of vascular injury. J Clin Invest 93: 652–661, 1994
Losordo DW, Pickering JG, Takeshita S, Leclerc G, Gal D, Weir L, Kearney M, Jekanowski J, Isner JM: Use of the rabbit ear artery to serially assess foreign protein secretion after site-specific arterial gene transfer in vivo. Evidence that anatomic identification of successful gene transfer may underestimate the potential magnitude of transgene expression. Circulation 89:785–792, 1994
Dichek DA, Neville RF, Zwiebel JA, Freeman SM, Leon MB, Anderson WF: Seeding of intravascular stents with genetically engineered endothelial cells. Circulation 80: 1347–1353, 1989
Plautz G, Nabel EG, Nabel GJ. Introduction of vascular smooth muscle cells expressing recombinant genes in vivo. Circulation 83: 578–583, 1991
Lynch CM, Clowes MM, Osborne WRA, Clowes AW, Miller AD: Long-term expression of human adenosine deaminase in vascular smooth muscle cells of rats: A model for gene therapy. Proc Natl Acad Sci USA 89:1138–1142, 1992
Flugelman MY, Jaklitsch MT, Newman KD, Casscells W, Bratthauer GL, Dichek DA: Low level in vivo gene transfer into the arterial wall through a perforated balloon catheter. Circulation 85: 1110–1117, 1992
Clowes MM, Lynch CM, Miller AD, Miller DG, Osborne WRA, Clowes AW: Long-term biological response of injured rat carotid ar-tery seeded with smooth muscle cells expressing retrovirally induced human genes. J Clin Invest 93: 644–651, 1994
Nabel EG, Pompili VJ, Plautz GE, Nabel GJ: Gene transfer and vascular disease. Cardiovasc Res 28: 445–455, 1994
Nabel EG, Nabel GJ: Complex models for the study of gene function in cardiovascular biology. Annu Rev Physiol 56: 741–761, 1994
Trapnell BC: Adenoviral vectors for gene transfer. Adv Drug Deliv Rev 12: 185–199, 1993
Schneider MD, French BA: The advent of adenovirus. Gene therapy for cardiovascular disease. Circulation 88: 1937–1942, 1993
Lemarchand P, Jones M, Yamada l, Crystal RG: In vivo gene transfer and expression in normal uninjured blood vessels using replication-deficient recombinant adenovirus vectors. Circ Res 72: 1132–1138, 1993
Guzman RJ, Lemarchand P, Crystal RG, Epstein SE, Finkel T: Efficient and selective adenovirus-mediated gene transfer into vascular neointima. Circulation 88: 2838–2848, 1993
Lee SW, Trapnell BC, Rade JJ, Virmani R, Dichek DA: In vivo adenoviral vector-mediated gene transfer into balloon-injured rat carotid arteries. Circ Res 73: 797–807, 1993
Rome JJ, Shayani V, Flugelman MY, Newman KD, Farb A, Virmani R, Dichek D: Anatomic barriers influence the distribution of in vivo gene transfer into the arterial wall. Modeling with microscopic tracer particles and verification with a recombinant adenoviral vector Arterioscler Thromb 14: 148–161, 1994
Willard JE, Landau C, Glamann B, Burns D, Jessen ME, Pirwitz MJ, Gerard RD, Meidell RS: Genetic modification of the vessel wall. Comparison of surgical and catheter-based techniques for delivery of recombinant adenovirus. Circulation 89: 2190–2197, 1994
Rome JJ, Shayani V, Newman KD, Farrell S, Lee SW, Virmani R, Dichek DA: Adenoviral vector-mediated gene transfer into sheep arteries using a double-balloon catheter. Hum Gene Ther 5: 1249–1258, 1994
Chang MW, Barr E, Seltzer J, Jiang Y-Q, Nabel GJ, Nabel EG, Parmacek MS, Leiden JF: Cytostatic gene therapy for vascular proliferative disorders with a constitutively active form of the retinoblastoma gene product. Science 267: 518–522, 1995
Schulick AH, Dong G, Newman KD, Virmani R, Dichek DA: Endothelium-specific in vivo gene transfer. Circ Res 77: 475–485, 1995
Schulick AH, Newman KD, Virmani R, Dichek DA: In vivo gene transfer into injured carotid arteries: optimization and evaluation of acute toxicity. Circulation 91: 2407–2414, 1995
Chang MW, Barr E, Lu, MM, Barton K, Leiden JM: Adenovirus-mediated over-expression of the cyclin/cyclin-dependent kinase inhibitor, p21 inhibits vascular smooth muscle cell proliferation and neointima formation in the rat carotid artery model of balloon angioplasty. J Clin Invest 96: 2260–2268, 1995
Barr E, Carroll J, Kalynych AM, Tripathy SK, Kozarsky K, Wilson JM, Leiden JM: Efficient catheter-mediated gene transfer into the heart using replication-defective adenovirus. Gene Ther 1: 51–58, 1994
French BA, Mazur W, Ali NM, Geske RS, Finnigan JP, Rodgers GP, Roberts R, Raizner AK: Percutaneous transluminal in vivo gene transfer by recombinant adenovirus in normal porcine coronary arteries, atherosclerotic arteries, and two models of coronary restenosis. Circulation 90:2402–2413, 1994
Ohno T, Gordon D, San H, Pompili VJ, Imperiale MJ, Nabel GJ, Nabel EG. Gene therapy for vascular smooth muscle cell proliferation after arterial injury. Science 265: 781–784, 1994
Steg PG, Feldman LJ, Scoazec J-Y, Tahlil O, Barry JJ, Boulechfar S, Ragot T, Isner JM, Perricaudet M: Arterial gene transfer to rabbit endothelial and smooth muscle cells using percutaneous delivery of an adenoviral vector. Circulation 90: 1648–1656, 1994
Landau C, Pirwitz MJ, Willard MA, Gerard RD, Meidell RS, Willard JE: Adenoviral mediated gene transfer to atherosclerotic arteries after balloon angioplasty. Am Heart J 129: 1051–1057, 1995
Feldman LJ, Steg PG, Zheng LP, Chen D, Kearney M, McGarr SE, Barry JJ, Dedieu J, Perricaudet M, Isner JM: Low-efficiency of percutaneous adenovirus-mediated gene transfer in atherosclerotic rabbit. J Clin Invest 95: 2662–2671, 1995
Li J-J, Ueno H, Tomita H, Yamamoto H, Kanegae Y, Saito I, Takeshita A: Adenovirus-mediated arterial gene transfer does not require prior injury for submaximal gene expression. Gene Ther 2: 351–354, 1995
Ueno H, Li J-J, Tomita H, Yamamoto H, Pan Y, Kanegae Y, Saito I, Takeshita A: Quantitative analysis of repeat adenovirus-mediated gene transfer into injured canine femoral arteries. Arterioscler Thromb Vase Biol 15: 2246–2253, 1995
Newman KD, Dunn PF, Owens JW, Schulick AH, Virmani R, Sukhova G, Libby P, Dichek DA: Adenovirus-mediated gene transfer into normal rabbit arteries results in prolonged vascular cell activation, inflammation, and neointima hyperplasia. J Clin Invest 96: 2955–2965, 1995
Muller DOOM, Gordon D, San H, Zhiyong Y, Pompili VJ, Nabel GJ, Nabel EG: Catheter-mediated pulmonary vascular gene transfer and expression. Circ Res 75: 1039–1049, 1994
Schachtner SK, Rome JJ, Hoyt RF Jr, Newman KD, Virmani R, Dichek DA: In vivo adenovirus-mediated gene transfer via the pulmonary artery of rats. Circ Res 76: 701–709, 1995
Lamping KG, Dole WP: Acute hypertension selectively potentiates constrictor responses of large coronary arteries to serotonin by altering endothelial function in vivo. Circ Res 61: 904–913, 1987
Rios CD, Ooboshi H, Piegors D, Davidson BL, Heistad DD: Adenovirus-mediated gene transfer to normal and atherosclerotic arteries: a novel approach. Arterioscler Thromb Vasc Biol 15: 2241–2245, 1995
Ooboshi H, Welsh MJ, Rios CD, Davidson BL, Heistad DD: Adenovirus-mediated gene transfer in vivo to cerebral blood vessels and perivascular tissue. Circ Res 77: 7–13, 1995
Rich DP, Couture LA, Cardoza LM, Guiggio VM, Armentano D, Espino PC, Hehir K, Welsh MJ, Smith AK, Gregory RJ: Development and analysis of recombinant adenoviruses for gene therapy of cystic fibrosis. Hum Gene Ther 4: 461–476, 1993
Zabner J, Couture LA, Smith AK, Welsh MJ: Correction of cAMP-stimulated fluid secretion in cystic fibrosis airway epithelia. Efficiency of adenovirus-mediated gene transfer in vitro. Hum Gene Ther 5: 585–593, 1994
Davidson BL, Allen ED, Kozarsky KF, Wilson JM, Roessler BJ: A model system for in vivo gene transfer into the central nervous system using adenoviral vector. Nat Genet 3: 219–223, 1993
Davidson BL, Doran SE, Shewach DS, Latta JM, Hartman JW, Roessler BJ: Expression of Escherichia coli β-galactosidase and rat HPRT in the CNS of Macaca mulatta following adenoviral mediated gene transfer. Exp Neurol 125: 258–267, 1994
Lal B, Cahan MA, Couraud P-O, Goldstein GW, Laterra J. Development of endogenous β-galactosidase and autofluorescence in rat brain microvessels. Implications for cell tracking and gene transfer studies. J Histochem Cytochem 42: 953–956, 1994
Edelman ER, Adams DH, Karnovsky MJ: Effect of controlled adventitial heparin delivery on smooth muscle cell proliferation following endothelial injury. Proc Natl Acad Sci 87: 3773–3777, 1990
Okada T, Bark DH, Mayberg MR: Localized release of perivascular heparin inhibits intimal proliferation after endothelial injury without systemic anticoagulation. Neurosurgery 25: 892–898, 1989
Okada T, Bark DH, Mayberg MR: Local anticoagulation without systemic effect using a polymer heparin delivery system. Stroke 19: 1470–1476, 1988
Edelman ER, Nugent MA, Karnovsky MJ: Perivascular and intravenous administration of basic fibroblast growth factor. Vascular and solid organ deposition. Proc Natl Acad Sci 90: 1513–1517, 1993
Villa AK, Guzman LA, Chen W, Golomb G, Levy RJ, Topol EJ: Local delivery of dexamethasone for prevention of neointimal proliferation in a rat model of balloon angioplasty. J Clin Invest 93: 1243–1249, 1994
Tedgui A, Lever MJ: The interaction of convection and diffusion in the transport of 131-I-albumin within the media of the rabbit thoracic aorta. Circ Res 57: 856–863, 1985
Simons M, Edelman ER, DeKeyser J, Langer R, Rosenberg RD: Antisense c-myb oligonucleotides inhibit arterial smooth muscle cell accumulation in vivo. Nature 359: 67–70, 1992
Engelhardt JF, Ye X, Doranz B, Wilson JM: Ablation of E2A in recombinant adenovirus improves transgene persistence and decreases inflammatory response in mouse liver. Proc Natl Acad Sci USA 91: 6196–6200, 1994
Fang B, Eisensmith RC, Wang H, Kay MA, Cross RE, Landen CN, Gordon G, Bellinger DA, Read MS, Hu PC, Brinkhous KM, Wool SLC: Gene therapy for hemophilia B: Host immunosuppression prolongs the therapeutic effect of adenovirus-mediated factor IX expression. Hum Gene Ther 6: 1039–1044, 1995
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Ooboshi, H., Ríos, C.D., Heistad, D.D. (1997). Novel methods for adenovirus-mediated gene transfer to blood vessels in vivo . In: Pierce, G.N., Claycomb, W.C. (eds) Novel Methods in Molecular and Cellular Biochemistry of Muscle. Developments in Molecular and Cellular Biochemistry, vol 20. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-6353-2_4
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