Published online before print May 12, 2003, doi: 10.1161/01.CIR.0000070540.80780.92
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2003;107:2677.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Safety and Feasibility of Catheter-Based Local Intracoronary Vascular Endothelial Growth Factor Gene Transfer in the Prevention of Postangioplasty and In-Stent Restenosis and in the Treatment of Chronic Myocardial Ischemia
Phase II Results of the Kuopio Angiogenesis Trial (KAT)
From A.I. Virtanen Institute, University of Kuopio (M.H., O.N., S.Y.-H.); the Department of Medicine, Kuopio University Hospital (M.H., J.H., A.H., A.K., S.S., A.R., K.P., M.L., S.Y.-H.), and the Department of Cardiology, University of Helsinki and Helsinki University Central Hospital (M.S., J.S., M.S.N.); the Department of Clinical Physiology and Nuclear Medicine (E.V., H.M., E.K., S.S.,) and the Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland (S.Y.-H.).
Correspondence to Dr Seppo Ylä-Herttuala, A.I. Virtanen Institute, University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland. E-mail Seppo.YlaHerttuala{at}uku.fi
Background— Catheter-based intracoronary vascular endothelial growth factor (VEGF) gene transfer is a potential treatment for coronary heart disease. However, only limited data are available about local VEGF gene transfer given during angioplasty (PTCA) and stenting.
Methods and Results— Patients with coronary heart disease (n=103; Canadian Cardiovascular Society class II to III; mean age, 58±6 years) were recruited in this randomized, placebo-controlled, double-blind phase II study. PTCA was performed with standard methods, followed by gene transfer with a perfusion-infusion catheter. Ninety percent of the patients were given stents; 37 patients received VEGF adenovirus (VEGF-Adv, 2x1010 pfu), 28 patients received VEGF plasmid liposome (VEGF-P/L; 2000 µg of DNA with 2000 µL of DOTMA:DOPE [1:1 wt/wt]), and 38 control patients received Ringer’s lactate. Follow-up time was 6 months. Gene transfer to coronary arteries was feasible and well tolerated. The overall clinical restenosis rate was 6%. In quantitative coronary angiography analysis, the minimal lumen diameter and percent of diameter stenosis did not significantly differ between the study groups. However, myocardial perfusion showed a significant improvement in the VEGF-Adv-treated patients after the 6-month follow-up. Some inflammatory responses were transiently present in the VEGF-Adv group, but no increases were detected in the incidences of serious adverse events in any of the study groups.
Conclusions— Gene transfer with VEGF-Adv or VEGF-P/L during PTCA and stenting shows that (1) intracoronary gene transfer can be performed safely (no major gene transfer-related adverse effects were detected), (2) no differences in clinical restenosis rate or minimal lumen diameter were present after the 6-month follow-up, and (3) a significant increase was detected in myocardial perfusion in the VEGF-Adv-treated patients.
Key Words: cardiovascular diseases • gene therapy • angioplasty • stents • perfusion
Related Article:
Circulation 2003 107: 2635-2637.
This article has been cited by other articles:
 |
|
 |
|
  M. Huang, D. A. Chan, F. Jia, X. Xie, Z. Li, G. Hoyt, R. C. Robbins, X. Chen, A. J. Giaccia, and J. C. Wu Short Hairpin RNA Interference Therapy for Ischemic Heart Disease Circulation, September 30, 2008; 118(14_suppl_1): S226 - S233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Higuchi, F. M. Bengel, S. Seidl, P. Watzlowik, H. Kessler, R. Hegenloh, S. Reder, S. G. Nekolla, H. J. Wester, and M. Schwaiger Assessment of {alpha}v{beta}3 integrin expression after myocardial infarction by positron emission tomography Cardiovasc Res, May 1, 2008; 78(2): 395 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Horvath and Y. Zhou Transmyocardial Laser Revascularization and Extravascular Angiogenetic Techniques to Increase Myocardial Blood Flow Card. Surg. Adult, January 1, 2008; 3(2008): 733 - 752. [Full Text]
|
|
|
|
 |
|
 K. Egashira, K. Nakano, K. Ohtani, K. Funakoshi, G. Zhao, Y. Ihara, J.-i. Koga, S. Kimura, R. Tominaga, and K. Sunagawa Local Delivery of Anti-Monocyte Chemoattractant Protein-1 by Gene-Eluting Stents Attenuates In-Stent Stenosis in Rabbits and Monkeys Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2563 - 2568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Wu, F. M. Bengel, and S. S. Gambhir Cardiovascular Molecular Imaging Radiology, August 1, 2007; 244(2): 337 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Vartanian and R. Sarkar Therapeutic Angiogenesis Vascular and Endovascular Surgery, July 1, 2007; 41(3): 173 - 185. [Abstract] [PDF]
|
|
|
|
 |
|
 C. Kupatt, R. Hinkel, M.-L. von Bruhl, T. Pohl, J. Horstkotte, P. Raake, C. El Aouni, E. Thein, S. Dimmeler, O. Feron, et al. Endothelial Nitric Oxide Synthase Overexpression Provides a Functionally Relevant Angiogenic Switch in Hibernating Pig Myocardium J. Am. Coll. Cardiol., April 10, 2007; 49(14): 1575 - 1584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yla-Herttuala, T. T. Rissanen, I. Vajanto, and J. Hartikainen Vascular Endothelial Growth Factors: Biology and Current Status of Clinical Applications in Cardiovascular Medicine J. Am. Coll. Cardiol., March 13, 2007; 49(10): 1015 - 1026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nikol Viral or non-viral angiogenesis gene transfer-New answers to old questions Cardiovasc Res, February 1, 2007; 73(3): 443 - 445. [Full Text] [PDF]
|
|
|
|
|
|
X. Hao, A. Mansson-Broberg, K.-H. Grinnemo, A. J. Siddiqui, G. Dellgren, L. A. Brodin, and C. Sylven Myocardial angiogenesis after plasmid or adenoviral VEGF-A165 gene transfer in rat myocardial infarction model Cardiovasc Res, February 1, 2007; 73(3): 481 - 487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. K. Salem, P. Ranjzad, A. Driessen, C. E. Appleby, A. M. Heagerty, and P. A. Kingston Beta-Adrenoceptor Blockade Markedly Attenuates Transgene Expression From Cytomegalovirus Promoters Within the Cardiovascular System Arterioscler. Thromb. Vasc. Biol., October 1, 2006; 26(10): 2267 - 2274. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Ripa, Y. Wang, E. Jorgensen, H. E. Johnsen, B. Hesse, and J. Kastrup Intramyocardial injection of vascular endothelial growth factor-A165 plasmid followed by granulocyte-colony stimulating factor to induce angiogenesis in patients with severe chronic ischaemic heart disease Eur. Heart J., August 1, 2006; 27(15): 1785 - 1792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Iwama, S. Uemura, N. Naya, K.-i. Imagawa, Y. Takemoto, O. Asai, K. Onoue, S. Okayama, S. Somekawa, Y. Kida, et al. Cardiac Expression of Placental Growth Factor Predicts the Improvement of Chronic Phase Left Ventricular Function in Patients With Acute Myocardial Infarction J. Am. Coll. Cardiol., April 18, 2006; 47(8): 1559 - 1567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ferrarini, N. Arsic, F. A. Recchia, L. Zentilin, S. Zacchigna, X. Xu, A. Linke, M. Giacca, and T. H. Hintze Adeno-Associated Virus-Mediated Transduction of VEGF165 Improves Cardiac Tissue Viability and Functional Recovery After Permanent Coronary Occlusion in Conscious Dogs Circ. Res., April 14, 2006; 98(7): 954 - 961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Cheema, T. Hong, N. Nili, A. Segev, J. G. Moffat, K. E. Lipson, A. R. Howlett, D. W. Holdsworth, M. J. Cole, B. Qiang, et al. Adventitial Microvessel Formation After Coronary Stenting and the Effects of SU11218, a Tyrosine Kinase Inhibitor J. Am. Coll. Cardiol., March 7, 2006; 47(5): 1067 - 1075. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Nordlie, L. E. Wold, B. Z. Simkhovich, C. Sesti, and R. A. Kloner Molecular Aspects of Ischemic Heart Disease: Ischemia/Reperfusion-Induced Genetic Changes and Potential Applications of Gene and RNA Interference Therapy Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2006; 11(1): 17 - 30. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Hanif, A. Patel, and J. Dunning Might gene therapy offer symptomatic relief for patients with 'no option' angina? Interactive CardioVascular and Thoracic Surgery, December 1, 2005; 4(6): 627 - 632. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Dulak, S. P Schwarzacher, R. H Zwick, H. Alber, G. Millonig, C. Weiss, H. Hugel, M. Frick, A. Jozkowicz, O. Pachinger, et al. Effects of local gene transfer of VEGF on neointima formation after balloon injury in hypercholesterolemic rabbits Vascular Medicine, November 1, 2005; 10(4): 285 - 291. [Abstract] [PDF]
|
|
|
|
|
|
R. Khurana, M. Simons, J. F. Martin, and I. C. Zachary Role of Angiogenesis in Cardiovascular Disease: A Critical Appraisal Circulation, September 20, 2005; 112(12): 1813 - 1824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tsutsumi and D. W. Losordo Double Face of VEGF Circulation, August 30, 2005; 112(9): 1248 - 1250. [Full Text] [PDF]
|
|
|
|
|
|
P. Leppanen, S. Koota, I. Kholova, J. Koponen, C. Fieber, U. Eriksson, K. Alitalo, and S. Yla-Herttuala Gene Transfers of Vascular Endothelial Growth Factor-A, Vascular Endothelial Growth Factor-B, Vascular Endothelial Growth Factor-C, and Vascular Endothelial Growth Factor-D Have No Effects on Atherosclerosis in Hypercholesterolemic Low-Density Lipoprotein-Receptor/Apolipoprotein B48-Deficient Mice Circulation, August 30, 2005; 112(9): 1347 - 1352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gyongyosi, A. Khorsand, S. Zamini, W. Sperker, C. Strehblow, J. Kastrup, E. Jorgensen, B. Hesse, K. Tagil, H. E. Botker, et al. NOGA-Guided Analysis of Regional Myocardial Perfusion Abnormalities Treated With Intramyocardial Injections of Plasmid Encoding Vascular Endothelial Growth Factor A-165 in Patients With Chronic Myocardial Ischemia: Subanalysis of the EUROINJECT-ONE Multicenter Double-Blind Randomized Study Circulation, August 30, 2005; 112(9_suppl): I-157 - I-165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Costa and D. I. Simon Molecular Basis of Restenosis and Drug-Eluting Stents Circulation, May 3, 2005; 111(17): 2257 - 2273. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Morishita, M. Aoki, and T. Ogihara Does gene therapy become pharmacotherapy? Exp Physiol, May 1, 2005; 90(3): 307 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kastrup, E. Jorgensen, A. Ruck, K. Tagil, D. Glogar, W. Ruzyllo, H. E. Botker, D. Dudek, V. Drvota, B. Hesse, et al. Direct intramyocardial plasmid vascular endothelial growth factor-A165 gene therapy in patients with stable severe angina pectoris: A randomized double-blind placebo-controlled study: The Euroinject One trial J. Am. Coll. Cardiol., April 5, 2005; 45(7): 982 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Simons Angiogenesis: Where Do We Stand Now? Circulation, March 29, 2005; 111(12): 1556 - 1566. [Full Text] [PDF]
|
|
|
|
|
|
Y. Cao, A. Hong, H. Schulten, and M. J. Post Update on therapeutic neovascularization Cardiovasc Res, February 15, 2005; 65(3): 639 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.B. Bamford, S. Wood, and R.J. Shaw Standards for gene therapy clinical trials based on pro-active risk assessment in a London NHS Teaching Hospital Trust QJM, February 1, 2005; 98(2): 75 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chandiwal, V. Balasubramanian, Z. K. Baldwin, M. S. Conte, and L. B. Schwartz Gene Therapy for the Extension of Vein Graft Patency: A Review Vascular and Endovascular Surgery, January 1, 2005; 39(1): 1 - 14. [Abstract] [PDF]
|
|
|
|
|
|
A. H. Baker, A. Kritz, L. M. Work, and S. A. Nicklin Cell-selective viral gene delivery vectors for the vasculature Exp Physiol, January 1, 2005; 90(1): 27 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Weber, A. Schober, and A. Zernecke Chemokines: Key Regulators of Mononuclear Cell Recruitment in Atherosclerotic Vascular Disease Arterioscler. Thromb. Vasc. Biol., November 1, 2004; 24(11): 1997 - 2008. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Sharif, K. Daly, J. Crowley, and T. O'Brien Current status of catheter- and stent-based gene therapy Cardiovasc Res, November 1, 2004; 64(2): 208 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Shiojima and K. Walsh The Role of Vascular Endothelial Growth Factor in Restenosis: The Controversy Continues Circulation, October 19, 2004; 110(16): 2283 - 2286. [Full Text] [PDF]
|
|
|
|
|
|
K. Ohtani, K. Egashira, K.-i. Hiasa, Q. Zhao, S. Kitamoto, M. Ishibashi, M. Usui, S. Inoue, Y. Yonemitsu, K. Sueishi, et al. Blockade of Vascular Endothelial Growth Factor Suppresses Experimental Restenosis After Intraluminal Injury by Inhibiting Recruitment of Monocyte Lineage Cells Circulation, October 19, 2004; 110(16): 2444 - 2452. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Anton, C. Wittermann, R. Haubner, M. Simoes, S. Reder, B. Essien, B. Wagner, J. Henke, W. Erhardt, S. Noll, et al. Coexpression of Herpesviral Thymidine Kinase Reporter Gene and VEGF Gene for Noninvasive Monitoring of Therapeutic Gene Transfer: An In Vitro Evaluation J. Nucl. Med., October 1, 2004; 45(10): 1743 - 1746. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.M Rubanyi The design and preclinical testing of Ad5FGF-4 to treat chronic myocardial ischaemia Eur. Heart J. Suppl., September 1, 2004; 6(suppl_E): E12 - E17. [Abstract] [Full Text]
|
|
|
|
 |
|
 L. Ye, H. K Haider, S.-J. Jiang, and E. K. Sim Therapeutic Angiogenesis Using Vascular Endothelial Growth Factor Asian Cardiovasc Thorac Ann, June 1, 2004; 12(2): 173 - 181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Leppanen, J. Rutanen, M. O. Hiltunen, T. T. Rissanen, M. P. Turunen, T. Sjoblom, J. Bruggen, G. Backstrom, M. Carlsson, E. Buchdunger, et al. Oral Imatinib Mesylate (STI571/Gleevec) Improves the Efficacy of Local Intravascular Vascular Endothelial Growth Factor-C Gene Transfer in Reducing Neointimal Growth in Hypercholesterolemic Rabbits Circulation, March 9, 2004; 109(9): 1140 - 1146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Rutanen, T. T. Rissanen, J. E. Markkanen, M. Gruchala, P. Silvennoinen, A. Kivela, A. Hedman, M. Hedman, T. Heikura, M.-R. Orden, et al. Adenoviral Catheter-Mediated Intramyocardial Gene Transfer Using the Mature Form of Vascular Endothelial Growth Factor-D Induces Transmural Angiogenesis in Porcine Heart Circulation, March 2, 2004; 109(8): 1029 - 1035. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. Losordo, J. M. Isner, and L. J. Diaz-Sandoval Endothelial Recovery: The Next Target in Restenosis Prevention Circulation, June 3, 2003; 107(21): 2635 - 2637. [Full Text] [PDF]
|
|