Abstract
The cardiovascular application of gene transfer and therapy has three overlapping goals. First, it can be seen as a molecular tool to probe pathways and mechanisms that are difficult to elucidate by other means. Second, it is widely used in preclinical studies and a variety of cardiovascular disease models to find the most efficient and safe clinical applications. Lastly, it is increasingly being used in clinical trial settings, for example to attenuate restenosis and vascular graft failure in coronary and peripheral vascular disease. We provide a critical overview of all three spheres of gene therapy-related strategies in cardiovascular disease research.
Key Words
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Staessen JA, Wang J, Bianchi G, Birkenhager WH. Essential hypertension. Lancet 2003;361: 1629–1641.
Rader DJ, Cohen J, Hobbs HH. Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. J Clin Invest 2003;111:1795–1803.
Forough R, Koyama N, Hasenstab D, et al. Overexpression of tissue inhibitor of matrix metalloproteinase-1 inhibits vascular smooth muscle cell functions in vitro and in vivo. Circ Res 1996;79:812–820.
Cioffi L, Sturtz FG, Wittmer S, et al. A novel endothelial cell-based gene therapy platform for the in vivo delivery of apolipoprotein E. Gene Ther 1999;6,1153-1159.
Grossman M, Rader DJ, Muller DW, et al. A pilot study of ex vivo gene therapy for homozygous familial hypercholesterolaemia. Nat Med 1995;1:1148–1154.
Mann MJ, Whittemore AD, Donaldson MC, et al. Ex-vivo gene therapy of human vascular bypass grafts with E2F decoy: the PREVENT single-centre randomised, controlled trial. Lancet 1999;354:1493–1498.
Hu T, Baker AH, Zou Y, Newby AC, Xu Q. Local gene transfer of tissue inhibitor of metalloproteinase-2 influences vein graft remodeling in a mouse model. Arterioscler Thromb Vasc Biol 2001;21:1275–1280.
George SJ, Lloyd CT, Angelini GD, Newby AC, Baker AH. Inhibition of late vein graft neointima formation in human and porcine models by adenovirus-mediated overexpression of tissue inhibitor of metalloproteinase-3. Circulation 2000;101:296–304.
George SJ, Johnson JL, Angelini GD, Newby AC, Baker AH. Adenovirus-mediated gene transfer of the human TIMP-1 gene inhibits smooth muscle cell migration and neointimal formation in human saphenous vein. Hum Gene Ther 1998; 9:867–877.
Yla-Herttuala S, Martin JF. Cardiovascular gene therapy. Lancet 2000;355:213–222.
Pancetta CJ, Miyauchi K, Berry D, et al. A tissue-engineered stent for cell-based vascular gene transfer. Hum Gene Ther 2002;13:433–441.
Baim DS, Wahr D, George B, et al. Randomized trial of a distal embolic protection device during percutaneous intervention of saphenous vein aorto-coronary bypass grafts. Circulation 2002;105:1285–1290.
Tao N, Gao GP, Parr M, et al. Sequestration of adenoviral vector by Kupffer cells leads to a nonlinear dose response of transduction in liver. Mol Ther 2001;3:28–35.
Huard J, Lochmuller H, Acsadi G, Jani A, Massie B, Karpati G. The route of administration is a major determinant of the transduction efficiency of rat tissues by adenoviral recombinants. Gene Ther 1995;2: 107–115.
Koeberl DD, Alexander IE, Halbert CL, Russell DW, Miller AD. Persistent expression of human clotting factor IX from mouse liver after intravenous injection of adeno-associated virus vectors. Proc Natl Acad Sci USA 1997; 94:1426–1431.
Ohashi K, Park F, Kay MA. Role of hepatocyte derived hyperplasia in lentivirus-mediated liver transduction in vivo. Hum Gene Ther 2002;13:653–663.
Kamps JAAM, Morslet HWM, Swart PJ, Meijer DKF, Scherphof GL. Massive targeting of liposomes, surface modified with anionized albumins, to hepatic endothelial cells. Proc Natl Acad Sci USA 1997;94:11,681–11,685.
Kim I, Jozkowicz A, Piedra PA, Oka K, Chan L. Lifetime correction of genetic deficiency in mice with a single injection of helper-dependent adenoviral vector. Proc Natl Acad Sci USA 2001;98:13,282–13,287.
Merrick AF, Shewring LD, Sawyer GJ, Gustafsson KT, Fabre JW. Comparison of adenovirus gene transfer to vascular endothelial cells in cell culture, organ culture, and in vivo. Transplantation 1996;62: 1085–1089.
Lemarchand P, Jaffe HA, Danel C, et al. Adenovirus-mediated transfer of a recombinant human alpha 1-antitrypsin cDNA to human endothelial cells. Proc Natl Acad Sci USA 1992;89:6482–6486.
Lemarchand P, Jones M, Yamada I, Crystal RG. In vivo gene transfer and expression in normal uninjured blood vessels using replication-deficient recombinant adenovirus vectors. Circ Res 1993;72:1132–1138.
Channon KM, Qian H, Youngblood SA, et al. Acute host-mediated endothelial injury after adenoviral gene transfer in normal rabbit arteries: impact on transgene expression and endothelial function. Circ Res 1998;82: 1253–1262.
Kochanek S, Clemens PR, Mitani K, Chen HH, Chan S, Caskey CT. A new adenoviral vector: replacement of all viral coding sequences with 28 kb of DNA independently expressing both full-length dystrophin and beta-galactosidase. Proc Natl Acad Sci USA 1996;93:5731–5736.
Kotin RM, Siniscalco M, Samulski RJ, et al. Site-specific integration by adeno-associated virus. Proc Natl Acad Sci USA 1990;87:2211–2215.
Nakai H, Montini E, Fuess S, Storm TA, Grompe M, Kay MA. AAV serotype 2 vectors preferentially integrate into active genes in mice. Nat Genet 2003;34:297–302.
Kreppel F, Kochanek S. Long-term transgene expression in proliferating cells mediated by episomally maintained high-capacity adenovirus vectors. J Virol 2004;78:9–22.
Ehrhardt A, Xu H, Kay MA. Episomal persistence of recombinant adenoviral vector genomes during the cell cycle in vivo. J Virol 2003;77:7689–7695.
Lynch CM, Hara PS, Leonard JC, Williams JK, Dean RH, Geary RL. Adeno-associated virus vectors for vascular gene delivery. Circ Res 1997;80:497–505.
Xiao X, Li J, Samulski RJ. Efficient long-term gene transfer into mouse tissue of immunocompetent mice by adeno-associated virus vector. J Virol 1996;70:8098–8108
Kawada T, Nakazawa M, Nakauchi S, et al. Rescue of hereditary form of dilated cardiomyopathy by rAAV-mediated somatic gene therapy: amelioration of morphological findings, sarcolemmal permeability, cardiac performances, and the prognosis of TO-2 hamsters. Proc Natl Acad Sci USA 2002;99:901–906.
Shimpo M, Ikeda U, Maeda Y, et al. AAV-mediated VEGF gene transfer into skeletal muscle stimulates angiogenesis and improves blood flow in a rat hindlimb ischemia model. Cardiovasc Res 2002;53:993–1001.
Wagner JA, Nepomuceno IB, Messner AH, et al. A phase II, double-blind, randomized, placebocontrolled clinical trial of tgAAVCF using maxillary sinus delivery in patients with cystic fibrosis with antrostomies. Hum Gene Ther 2002;13:1349–1359.
Manno CS, Chew AJ, Hutchison S, et al. AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B. Blood 2003;101:2963–2972.
Miller DG, Adam MA, Miller AD. Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol Cell Biol 1990;10:4239–4242.
Hacein-Bey-Abina S, Von Kalle C, Schmidt M, et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 2003;302:415–419.
Dishart KL, Denby L, George SJ, et al. Third-generation lentivirus vectors efficiently transduce and phenotypically modify vascular cells: implications for gene therapy. J Mol Cell Cardiol 2003;35:739–748.
Roy I. Ethical considerations in the use of lentiviral vectors for genetic transfer. Somat Cell Mol Genet 2001;26:175–191.
Sandrin V, Russell SJ, Cosset FL. Targeting retroviral and lentiviral vectors. Curr Top Microbiol Immunol 2003;281:137–178.
Lawrie A, Brisken AF, Francis SE, et al. Ultrasound enhances reporter gene expression after transfection of vascular cells in vitro. Circulation 1999;99:2617–2620.
Lawrie A, Brisken AF, Francis SE, et al. Microbubble-enhanced ultrasound for vascular gene delivery. Gene Ther 2000;7:2023–2027.
Taniyama Y, Tachibana K, Hiraoka K, et al. Local delivery of plasmid DNA into rat carotid artery using ultrasound. Circulation 2002;105:1233–1239.
Stephan DJ, Yang ZY, San H, et al. A new cationic liposome DNA complex enhances the efficiency of arterial gene transfer in vivo. Hum Gene Ther 1996;7:1803–1812.
Asahara T, Chen D, Tsurumi Y, et al. Accelerated restitution of endothelial integrity and endothelium-dependent function after phVEGF165 gene transfer. Circulation 1996;94:3291–3302.
Tsurumi Y, Takeshita S, Chen D, et al. Direct intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor augments collateral development and tissue perfusion. Circulation 1996;94: 3281–3290.
Hackett NR, El Sawy T, Lee LY, et al. Use of quantitative TaqMan real-time PCR to track the time-dependent distribution of gene transfer vectors in vivo. Mol Ther 2000;2:649–656.
Bergelson JM, Cunningham JA, Droguett G, et al. Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 1997;275:1320–1323.
Tomko RP, Xu R, Philipson L. HCAR and MCAR: the human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses. Proc Natl Acad Sci USA 1997;94:3352–3356.
Wickham TJ, Mathias P, Cheresh DA, Nemerow GR. Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Cell 1993;73:309–319.
Wickham TJ, Filardo EJ, Cheresh DA, Nemerow GR. Integrin alpha v beta 5 selectively promotes adenovirus mediated cell membrane permeabilization. J Cell Biol 1994;127:257–264.
Dechecchi MC, Tamanini A, Bonizzato A, Cabrini G. Heparan sulfate glycosaminoglycans are involved in adenovirus type 5 and 2-host cell interactions. Virology 2000;268:382–390.
Smith TA, Idamakanti N, Rollence ML, et al. Adenovirus serotype 5 fiber shaft influences in vivo gene transfer in mice. Hum Gene Ther 2003;14:777–787.
Harari OA, Wickham TJ, Stocker CJ, et al. Targeting an adenoviral gene vector to cytokine-activated vascular endothelium via E-selectin. Gene Ther 1999;6:801–807.
Watkins SJ, Mesyanzhinov VV, Kurochkina LP, Hawkins RE. The ‘adenobody’ approach to viral targeting: specific and enhanced adenoviral gene delivery. Gene Ther 1997;4:1004–1012.
Nicklin SA, White SJ, Watkins SJ, Hawkins RE, Baker AH. Selective targeting of gene transfer to vascular endothelial cells by use of peptides isolated by phage display. Circulation 2000;102:231–237.
Nettelbeck DM, Miller DW, Jerome V, et al. Targeting of adenovirus to endothelial cells by a bispecific single-chain diabody directed against the adenovirus fiber knob domain and human endoglin (CD105). Mol Ther 2001; 3:882–891.
Reynolds PN, Zinn KR, Gavrilyuk VD, et al. A targetable, injectable adenoviral vector for selective gene delivery to pulmonary endothelium in vivo. Mol Ther 2000;2:562–578.
Nicklin SA, Reynolds PN, Brosnan MJ, et al. Analysis of cell-specific promoters for viral gene therapy targeted at the vascular endothelium. Hypertension 2001;38:65–70.
Reynolds PN, Nicklin SA, Kaliberova L, et al. Combined transductional and transcriptional targeting improves the specificity of transgene expression in vivo. Nat Biotechnol 2001;19:838–842.
Su EJ, Stevenson SC, Rollence M, Marshall-Neff J, Liau G. A genetically modified adenoviral vector exhibits enhanced gene transfer of human smooth muscle cells. J Vasc Res 2001;38:471–478.
Havenga MJ, Lemckert AA, Grimbergen JM, et al. Improved adenovirus vectors for infection of cardiovascular tissues. J Virol 2001;75:3335–3342.
Chillon M, Bosch A, Zabner J, et al. Group D adenoviruses infect primary central nervous system cells more efficiently than those from Group C. J Virol 1999;73:2537–2540.
Havenga MJ, Lemckert AA, Ophorst OJ, et al. Exploiting the natural diversity in adenovirus tropism for therapy and prevention of disease. J Virol 2002;76:4612–4620.
Xia D, Henry L, Gerard RD, Deisenhofer J. Structure of the receptor binding domain of adenovirus type 5 fiber protein. Curr Top Microbiol Immunol 1995;199:39–46.
Krasnykh V, Dmitriev I, Mikheeva G, Miller CR, Belousova N, Curiel DT. Characterization of an adenovirus vector containing a heterologous peptide epitope in the HI loop of the fiber knob. J Virol 1998;72: 1844–1852.
Pasqualini R, Koivunen E, Ruoslahti E. A peptide isolated from phage display libraries is a structural and functional mimic of an RGD-binding site on integrins. J Cell Biol 1995;130:1189–1196.
Dmitriev I, Krasnykh V, Miller CR, et al. An adenovirus vector with genetically modified fibers demonstrates expanded tropism via utilization of a coxsackievirus and adenovirus receptor-independent cell entry mechanism. J Virol 1998; 72:9706–9713.
Hay CM, De Leon H, Jafari JD, et al. Enhanced gene transfer to rabbit jugular veins by an adenovirus containing a cyclic RGD motif in the HI loop of the fiber knob. J Vasc Res 2001;38:315–323.
Vigne E, Mahfouz I, Dedieu JF, Brie A, Perricaudet M, Yeh P. RGD inclusion in the hexon monomer provides adenovirus type 5-based vectors with a fiber knob-independent pathway for infection. J Virol 1999;73: 5156–5161.
Xia H, Anderson B, Mao Q, Davidson BL. Recombinant human adenovirus: targeting to the human transferrin receptor improves gene transfer to brain microcapillary endothelium. J Virol 2000;74:11,359–11,366.
Work LM, Nicklin SA, Brain NJ, et al. Development of efficient viral vectors selective for vascular smooth muscle cells. Mol Ther 2004;9:198–208.
Nicklin SA, Von Seggern DJ, Work LM, Pek DC, Dominiczak AF, Nemerow GR, Baker AH. Ablating adenovirus type 5 fiber-CAR binding and HI loop insertion of the SIGYPLP peptide generate an endothelial cell-selective adenovirus. Mol Ther 2001;4:534–542.
Nicklin SA, White SJ, Nicol CG, Von Seggern DJ, Baker AH. In vitro and in vivo characterisation of endothelial cell selective adenoviral vectors. J Gene Med 2004;6:300–308.
Leissner P, Legrand V, Schlesinger Y, et al. Influence of adenoviral fiber mutations on viral encapsidation, infectivity and in vivo tropism. Gene Ther 2001;8:49–57.
Alemany R, Curiel DT. CAR-binding ablation does not change biodistribution and toxicity of adenoviral vectors. Gene Ther 2001;8:1347–1353.
Gao GP, Alvira MR, Wang L, Calcedo R, Johnston J, Wilson JM. Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc Natl Acad Sci USA 2002;99:11,854–11,859.
Girod A, Ried M, Wobus C, et al. Genetic capsid modifications allow efficient re-targeting of adenoassociated virus type 2. Nat Med 1999;5:1052–1056.
Nicklin SA, Buening H, Dishart KL, et al. Efficient and selective AAV2-mediated gene transfer directed to human vascular endothelial cells. Mol Ther 2001;4:174–181.
Xie Q, Bu W, Bhatia S, et al. The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy. Proc Natl Acad Sci USA 2002;99:10,405–10,410.
Kern A, Schmidt K, Leder C, et al. Identification of a heparin-binding motif on adeno-associated virus type 2 capsids. J Virol 2003;77:11,072–11,081.
Channon KM, Guzik TJ. Mechanisms of superoxide production in human blood vessels: relationship to endothelial dysfunction, clinical and genetic risk factors. J Physiol Pharmacol 2002;53:515–524.
Kerr S, Brosnan MJ, McIntyre M, Reid JL, Dominiczak AF, Hamilton CA. Superoxide anion production is increased in a model of genetic hypertension: role of the endothelium. Hypertension 1999;33:1353–1358.
Berry C, Hamilton CA, Brosnan MJ, et al. Investigation into the sources of superoxide in human blood vessels: angiotensin II increases superoxide production in human internal mammary arteries. Circulation 2000;101: 2206–2212.
Hamilton CA, Miller WH, Al-Benna S, et al. Strategies to reduce oxidative stress in cardiovascular disease. Clin Sci (Lond) 2004;106:219–234.
Alexander MY, Brosnan MJ, Hamilton CA, et al. Gene transfer of endothelial nitric oxide synthase but not Cu/Zn superoxide dismutase restores nitric oxide availability in the SHRSP. Cardiovasc Res 2000;47:609–617.
Fennell JP, Brosnan MJ, Frater AJ,. Adenovirus-mediated overexpression of extracellular superoxide dismutase improves endothelial dysfunction in a rat model of hypertension. Gene Ther 2002;9:110–117
Nakane H, Miller FJ, Faraci FM, Toyoda K, Heistad DD. Gene transfer of endothelial nitric oxide synthase reduces angiotensin II-induced endothelial dysfunction. Hypertension 2000;35:595–601
Kishi T, Hirooka Y, Ito K, Sakai K, Shimokawa G, Takeshita A. Cardiovascular effects of overexpression of endothelial nitric oxide synthase in the rostral ventrolateral medulla in stroke-prone spontaneously hypertensive rats. Hypertension 2002;39:264–268.
Zhang JJ, Wang C, Lin KF, Chao L, Chao J. Human tissue kallikrein attenuates hypertension and secretes into circulation and urine after intramuscular gene delivery in hypertensive rats. Clin Exp Hypertens 1999;21: 1145–1160.
Lin KF, Chao L, Chao J. Prolonged reduction of high blood pressure with human nitric oxide synthase gene delivery. Hypertension 1997;30:307–313.
Chu Y, Iida S, Lund DD, et al. Gene transfer of extracellular superoxide dismutase reduces arterial pressure in spontaneously hypertensive rats: role of heparin-binding domain. Circ Res 2003;92:461–468.
Phillips MI, Mohuczy D, Coffey M, et al. Prolonged reduction of high blood pressure with an in vivo, nonpathogenic, adeno-associated viral vector delivery of AT1-R mRNA antisense. Hypertension 1997;29: 374–380
Dominiczak AF, Negrin DC, Clark JS, Brosnan MJ, McBride MW, Alexander MY. Genes and hypertension: from gene mapping in experimental models to vascular gene transfer strategies. Hypertension 2000;35:164–172.
Zheng JS, Yang XQ, Lookingland KJ, et al. Gene transfer of human guanosine 5′-triphosphate cyclohydrolase I restores vascular tetrahydrobiopterin level and endothelial function in low rennin hypertension. Circulation 2003;108:1238–1245.
Lee WK, Padmanabhan S, Dominiczak AF. Genetics of hypertension: from experimental models to clinical applications. J Hum Hypertens 2000;14:631–647.
McBride MW, Carr FJ, Graham D, et al. Microarray analysis of rat chromosome 2 congenic strains. Hypertension 2003;41:847–853.
Baker AH, Mehta D, George SJ, Angelini GD. Prevention of vein graft failure: potential applications for gene therapy. Cardiovasc Res 1997;35:442–450.
Kibbe MR, Billiar TR, Tzeng E. Gene therapy for restenosis. Circ Res 2000;86:829–833.
West NEJ, Qian H, Guzik TJ, et al. Nitric oxide synthase (nNOS) gene transfer modifies venous bypass graft remodeling. Effects on vascular smooth muscle cell differentiation and superoxide production. Circulation 2001;104:1526–2532.
George SJ, Angelini GS, Capogrossi MC, Baker AH. Wild-type p53 gene transfer inhibits neointima formation in human saphenous vein by modulation of smooth muscle cell migration and induction of apoptosis. Gene Ther 2001; 8:668–676.
Schwartz LB, Moawad J, Svensson EC, et al. Adenoviral-mediated gene transfer of a constitutively active form of the retinoblastoma gene product attenuates neointimal thickening in experimental vein grafts. J Vasc Surg 1999; 29:874–881.
Ohno N, Itoh H, Ikeda T, et al. Accelerated reendothelialization with suppressed thrombogenic property and neointimal hyperplasia of rabbit jugular vein grafts by adenovirus-mediated gene transfer of C-type natriuretic peptide. Circulation 2002;105:1623–1626.
Wan S, George SJ, Nicklin SA, Yim APC, Baker AH. Overexpression of p53 increases lumen size and blocks neointima formation in porcine interposition vein grafts. Mol Ther 2004;9:689–698.
Herz J, Gerard RD. Adenovirus-mediated transfer of low density lipoprotein receptor gene acutely accelerates cholesterol clearance in normal mice. Proc Natl Acad Sci USA 1993;90:2812–2816.
Kozarsky KF, Jooss K, Donahee M, Strauss JF 3rd, Wilson JM. Effective treatment of familial hypercholesterolaemia in the mouse model using adenovirus-mediated transfer of the VLDL receptor gene. Nat Genet 1996;13:54–62.
Stevenson SC, Marshall-Neff J, Teng B, Lee CB, Roy S, McClelland A. Phenotypic correction of hypercholesterolemia in apoE-deficient mice by adenovirus-mediated in vivo gene transfer. Arterioscler Thromb Vasc Biol 1995;15:479–84.
Grossman M, Raper SE, Kozarsky K, et al. Successful ex vivo gene therapy directed to liver in a patient with familial hypercholesterolaemia. Nat Genet 1994;6:335–341.
Oka K, Pastore L, Kim IH, Merched A, Nomura S, Lee HJ, Merched-Sauvage M, Arden-Riley C, Lee B, Finegold M, Beaudet A, Chan L. Long-term stable correction of low-density lipoprotein receptordeficient mice with a helper-dependent adenoviral vector expressing the very low-density lipoprotein receptor. Circulation 2001; 103: 1274–1281.
Laitinen M, Makinen K, Manninen H, et al. Adenovirus-mediated gene transfer to lower limb artery of patients with chronic critical leg ischemia. Hum Gene Ther 1998;9:1481–1486.
Fan L, Drew J, Dunckley MG, Owen JS, Dickson G. Efficient coexpression and secretion of antiatherogenic human apolipoprotein AI and lecithin-cholesterol acyltransferase by cultured muscle cells using adeno-associated virus plasmid vectors. Gene Ther 1998;5:1434–1440.
Juan SH, Lee TS, Tseng KW, et al. Adenovirus-mediated heme oxygenase-1 gene transfer inhibits the development of atherosclerosis in apolipoprotein E-deficient mice. Circulation 2001;104:1519–1525.
Losordo DW, Vale PR, Symes JF, et al. Gene therapy for myocardial angiogenesis—initial clinical results with direct myocardial injection of phVEGF(165) as sole therapy for myocardial ischaemia. Circulation 1998; 98: 2800–2804.
Baumgartner I, Pieczek A, Manor O, et al. Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation 1998; 97: 1114–1123.
Gowdak LHW, Poliakova L, Wang X, et al. Adenovirus-mediated VEGF121 gene transfer stimulates angiogenesis in normoperfused skeletal muscle and preserves tissue perfusion after induction of ischemia. Circulation 2000; 102:565–571.
Rajagopalan S, Shah M, Luciano A, Crystal R, Nabel EG. Adenovirus-mediated gene transfer of VEGF121 improves lower-extremity endothelial function and flow reserve. Circulation 2001;104:753–755.
Rosengart TK, Lee LY, Patel SR, et al. Angiogenesis gene therapy. Phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease. Circulation 1999;100:468–474.
Grines CL, Watkins MW, Helmer G, et al. Angiogenic gene therapy (AGENT) trial in patients with stable angina pectoris. Circulation 2002;105:1291–1297.
Grines CL, Watkins MW, Mahmarian JJ, et al., Angiogene GENe Therapy (AGENT-2) Study Group. A randomized, double-blind, placebo-controlled trial of Ad5FGF-4 gene therapy and its effect on myocardial perfusion in patients with stable angina. J Am Coll Cardiol 2003;42:1339–1347.
Celletti, FL, Waugh JM, Amabile PG, Brendolan A, Hilfiker PR, Dake MD. Vascular endothelial growth factor enhances atherosclerotic plaque progression. Nat Med 2001;7:425–429.
Springer ML, Chen AS, Kraft PE, Bednarski M, Blau HM. VEGF gene delivery to muscle: potential role for vasculogenesis in adults. Mol Cell 1998;2:549–548.
Lee RJ, Springer ML, Blanco-Bose WE, Shaw R, Ursell PC, Blau HM. VEGF gene delivery to myocardium. Deleterious effects of unregulated expression. Circulation 2000;102:898–901.
Ozawa CR, Banfi A, Glazer NL, et al. Microenvironmental VEGF concentration, not total dose, determines a threshold between normal and aberrant angiogenesis. J Clin Invest 2004;113:516–527.
Wheeler MD, Katuna M, Smutney OM, et al. Comparison of the effect of adenoviral delivery of three superoxide dismutase genes against hepatic ischaemia-reperfusion injury. Hum Gene Ther 2001;12:2167–2177.
Melo LG, Agrawal R, Zhang LN, et al. Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene. Circulation 2002;105:602–607.
Phillips MI, Tang Y, Schmidt-Ott K, Qian KP, Kagiyama S. Vigilant vector: heart-specific promoter in an adeno-associated virus vector for cardioprotection. Hypertension 2002;39:651–655.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Humana Press Inc.
About this chapter
Cite this chapter
Miller, W.H., Nicklin, S.A., Baker, A.H., Dominiczak, A.F. (2005). Gene Transfer and the Cardiovascular System. In: Rai, M.K., Paton, J.F.R., Kasparov, S., Katovich, M.J. (eds) Cardiovascular Genomics. Contemporary Cardiology. Humana Press. https://doi.org/10.1385/1-59259-883-8:175
Download citation
DOI: https://doi.org/10.1385/1-59259-883-8:175
Publisher Name: Humana Press
Print ISBN: 978-1-58829-400-5
Online ISBN: 978-1-59259-883-0
eBook Packages: MedicineMedicine (R0)