Circulation. 2001;104:2710-2715
doi: 10.1161/hc4701.099585
doi: 10.1161/hc4701.099585
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2001;104:2710.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Adenovirus-Mediated Heme Oxygenase-1 Gene Delivery Inhibits Injury-Induced Vascular Neointima Formation
From the Departments of Medicine (D.A.T., W.D., X.L., A.J.E., A.I.S.) and Pharmacology (W.D.), Baylor College of Medicine, and Veterans Affairs Medical Center (W.D., K.J.P., A.I.S.), Houston, Tex.
Correspondence to Andrew I. Schafer, MD, Department of Medicine, Baylor College of Medicine, 6550 Fannin, SM MS 1423, Houston, TX 77030. E-mail aschafer{at}bcm.tmc.edu
Background— Recent studies have demonstrated that systemic pharmacological induction of heme oxygenase-1 (HO-1), the inducible isoform of the initial and rate-limiting enzyme for heme catabolism, attenuates neointima formation after experimental vascular injury. We have now investigated the ability of localized adenovirus-mediated HO-1 (Ad-HO-1) gene delivery to modify arterial remodeling after balloon angioplasty.
Methods and Results— Two weeks after balloon angioplasty in the rat carotid artery, elevated HO-1 protein was observed in the Ad-HO-1 arteries compared with those exposed to empty adenovirus (Ad-E) or to PBS. The arteries exposed to Ad-HO-1 exhibited significantly reduced neointimal area, medial wall area, neointimal area/medial wall area ratio, and neointimal thickness compared with arteries exposed to Ad-E. The Ad-E vessels showed subtle reductions in each morphometric parameter compared with PBS vessels. In a separate group of animals, concomitant treatment of Ad-HO-1 with the HO-1 inhibitor tin protoporphyrin completely restored each morphometric parameter to control levels. Arteries exposed to Ad-HO-1 demonstrated significantly increased TUNEL labeling of apoptotic nuclei and significantly decreased PCNA labeling of DNA synthesis in the medial wall 48 hours after injury.
Conclusions— These results indicate that HO-1 represents an important in vivo vasoprotective mediator that is capable of attenuating the pathophysiological remodeling response to endovascular injury and suggest that HO-1 may be a novel target for the treatment of vascular disease.
Key Words: viruses • arteries • neointima • heme oxygenase
This article has been cited by other articles:
 |
|
 |
|
  A.-L. Levonen, E. Vahakangas, J. K. Koponen, and S. Yla-Herttuala Antioxidant Gene Therapy for Cardiovascular Disease: Current Status and Future Perspectives Circulation, April 22, 2008; 117(16): 2142 - 2150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Datla, G. J. Dusting, T. A. Mori, C. J. Taylor, K. D. Croft, and F. Jiang Induction of Heme Oxygenase-1 In Vivo Suppresses NADPH Oxidase Derived Oxidative Stress Hypertension, October 1, 2007; 50(4): 636 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C.M. Siow and A. T. Churchman Adventitial growth factor signalling and vascular remodelling: Potential of perivascular gene transfer from the outside-in Cardiovasc Res, September 1, 2007; 75(4): 659 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Hill-Kapturczak and A. Agarwal Haem oxygenase-1--a culprit in vascular and renal damage? Nephrol. Dial. Transplant., June 1, 2007; 22(6): 1495 - 1499. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Tiroch, W. Koch, N. von Beckerath, A. Kastrati, and A. Schomig Heme oxygenase-1 gene promoter polymorphism and restenosis following coronary stenting Eur. Heart J., April 2, 2007; 28(8): 968 - 973. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-L. Levonen, M. Inkala, T. Heikura, S. Jauhiainen, H.-K. Jyrkkanen, E. Kansanen, K. Maatta, E. Romppanen, P. Turunen, J. Rutanen, et al. Nrf2 Gene Transfer Induces Antioxidant Enzymes and Suppresses Smooth Muscle Cell Growth In Vitro and Reduces Oxidative Stress in Rabbit Aorta In Vivo Arterioscler. Thromb. Vasc. Biol., April 1, 2007; 27(4): 741 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-m. Liu, M. A. Azam, K. J. Peyton, D. Ensenat, A. N. Keswani, H. Wang, and W. Durante Butylated hydroxyanisole stimulates heme oxygenase-1 gene expression and inhibits neointima formation in rat arteries Cardiovasc Res, April 1, 2007; 74(1): 169 - 179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Stocker and M. A. Perrella Heme Oxygenase-1: A Novel Drug Target for Atherosclerotic Diseases? Circulation, November 14, 2006; 114(20): 2178 - 2189. [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Schaer, G. Schoedon, A. Imhof, M. O. Kurrer, and D. J. Schaer Constitutive Endocytosis of CD163 Mediates Hemoglobin-Heme Uptake and Determines the Noninflammatory and Protective Transcriptional Response of Macrophages to Hemoglobin Circ. Res., October 27, 2006; 99(9): 943 - 950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Brunt, K. K. Fenrich, G. Kiani, M. Yat Tse, S. C. Pang, C. A. Ward, and L. G. Melo Protection of Human Vascular Smooth Muscle Cells From H2O2-Induced Apoptosis Through Functional Codependence Between HO-1 and AKT Arterioscler. Thromb. Vasc. Biol., September 1, 2006; 26(9): 2027 - 2034. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yano, R. Ozono, Y. Oishi, M. Kambe, M. Yoshizumi, T. Ishida, S. Omura, T. Oshima, and K. Igarashi Genetic ablation of the transcription repressor Bach1 leads to myocardial protection against ischemia/reperfusion in mice. Genes Cells, July 1, 2006; 11(7): 791 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Wu, K. Kathir, P. K. Witting, K. Beck, K. Choy, C. Li, K. D. Croft, T. A. Mori, D. Tanous, M. R. Adams, et al. Antioxidants protect from atherosclerosis by a heme oxygenase-1 pathway that is independent of free radical scavenging J. Exp. Med., April 17, 2006; 203(4): 1117 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. W. Ryter, J. Alam, and A. M. K. Choi Heme Oxygenase-1/Carbon Monoxide: From Basic Science to Therapeutic Applications Physiol Rev, April 1, 2006; 86(2): 583 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. F. Granada, D. Ensenat, A. N. Keswani, G. L. Kaluza, A. E. Raizner, X.-m. Liu, K. J. Peyton, M. A. Azam, H. Wang, and W. Durante Single Perivascular Delivery of Mitomycin C Stimulates p21 Expression and Inhibits Neointima Formation in Rat Arteries Arterioscler. Thromb. Vasc. Biol., November 1, 2005; 25(11): 2343 - 2348. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. J. Dzau, M. Gnecchi, and A. S. Pachori Enhancing Stem Cell Therapy Through Genetic Modification J. Am. Coll. Cardiol., October 4, 2005; 46(7): 1351 - 1353. [Full Text] [PDF]
|
|
|
|
|
|
T. Morita Heme Oxygenase and Atherosclerosis Arterioscler. Thromb. Vasc. Biol., September 1, 2005; 25(9): 1786 - 1795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Nakao, N. Murase, C. Ho, H. Toyokawa, T. R. Billiar, and S. Kanno Biliverdin Administration Prevents the Formation of Intimal Hyperplasia Induced by Vascular Injury Circulation, July 26, 2005; 112(4): 587 - 591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Li, K. Tanaka, K. Morioka, T. Uesaka, N. Yamada, A. Takamori, M. Handa, S. Tanabe, and A. Ihaya Thymidine Phosphorylase Gene Transfer Inhibits Vascular Smooth Muscle Cell Proliferation by Upregulating Heme Oxygenase-1 and p27KIP1 Arterioscler. Thromb. Vasc. Biol., July 1, 2005; 25(7): 1370 - 1375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Liu, Z.-Q. Chen, G. C. Bobustuc, J. M. McNatt, H. Segall, S. Pan, J. T. Willerson, and P. Zoldhelyi Local Gene Transduction of Cyclooxygenase-1 Increases Blood Flow in Injured Atherosclerotic Rabbit Arteries Circulation, April 12, 2005; 111(14): 1833 - 1840. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Omura, H. Suzuki, M. Toyofuku, R. Ozono, N. Kohno, and K. Igarashi Effects of genetic ablation of bach1 upon smooth muscle cell proliferation and atherosclerosis after cuff injury Genes Cells, March 1, 2005; 10(3): 277 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fu, J. Zhang, Y.-H. Tseng, T. Cui, X. Zhu, Y. Xiao, Y. Mou, H. De Leon, M. M.J. Chang, Y. Hamamori, et al. Rad GTPase Attenuates Vascular Lesion Formation by Inhibition of Vascular Smooth Muscle Cell Migration Circulation, March 1, 2005; 111(8): 1071 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.G Melo, M Gnecchi, A.S Pachori, K Wang, and V.J Dzau Gene- and cell-based therapies for cardiovascular diseases: current status and future directions Eur. Heart J. Suppl., September 1, 2004; 6(suppl_E): E24 - E35. [Abstract] [Full Text]
|
|
|
|
|
|
D. Kong, L. G. Melo, A. A. Mangi, L. Zhang, M. Lopez-Ilasaca, M. A. Perrella, C. C. Liew, R. E. Pratt, and V. J. Dzau Enhanced Inhibition of Neointimal Hyperplasia by Genetically Engineered Endothelial Progenitor Cells Circulation, April 13, 2004; 109(14): 1769 - 1775. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-H. Chen, L.-Y. Chau, M.-W. Lin, L.-C. Chen, M.-H. Yo, J.-W. Chen, and S.-J. Lin Heme oxygenase-1 gene promotor microsatellite polymorphism is associated with angiographic restenosis after coronary stenting Eur. Heart J., January 1, 2004; 25(1): 39 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. D. T. G. Wagener, H.-D. Volk, D. Willis, N. G. Abraham, M. P. Soares, G. J. Adema, and C. G. Figdor Different Faces of the Heme-Heme Oxygenase System in Inflammation Pharmacol. Rev., September 1, 2003; 55(3): 551 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhang, P. Shan, J. Alam, R. J. Davis, R. A. Flavell, and P. J. Lee Carbon Monoxide Modulates Fas/Fas Ligand, Caspases, and Bcl-2 Family Proteins via the p38{alpha} Mitogen-activated Protein Kinase Pathway during Ischemia-Reperfusion Lung Injury J. Biol. Chem., June 6, 2003; 278(24): 22061 - 22070. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. P. Griese, S. Achatz, C. A. Batzlsperger, U. G. Strauch, B. Grumbeck, J. Weil, and G. A.J. Riegger Vascular gene delivery of anticoagulants by transplantation of retrovirally-transduced endothelial progenitor cells Cardiovasc Res, May 1, 2003; 58(2): 469 - 477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Visner, F. Lu, H. Zhou, J. Liu, K. Kazemfar, and A. Agarwal Rapamycin Induces Heme Oxygenase-1 in Human Pulmonary Vascular Cells: Implications in the Antiproliferative Response to Rapamycin Circulation, February 18, 2003; 107(6): 911 - 916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Tulis, Z. H. Mnjoyan, R. L. Schiesser, H. S. Shelat, A. J. Evans, P. Zoldhelyi, and K. Fujise Adenoviral Gene Transfer of Fortilin Attenuates Neointima Formation Through Suppression of Vascular Smooth Muscle Cell Proliferation and Migration Circulation, January 7, 2003; 107(1): 98 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. K. Nakahashi, K. Hoshina, P. S. Tsao, E. Sho, M. Sho, J. K. Karwowski, C. Yeh, R.-B. Yang, J. N. Topper, and R. L. Dalman Flow Loading Induces Macrophage Antioxidative Gene Expression in Experimental Aneurysms Arterioscler. Thromb. Vasc. Biol., December 1, 2002; 22(12): 2017 - 2022. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Durante Carbon monoxide and bile pigments: surprising mediators of vascular function Vascular Medicine, August 1, 2002; 7(3): 195 - 202. [Abstract] [PDF]
|
|
|
|
 |
|
 D. Morse and A. M. K. Choi Heme Oxygenase-1 . The "Emerging Molecule" Has Arrived Am. J. Respir. Cell Mol. Biol., July 1, 2002; 27(1): 8 - 16. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. D. Lucca, J. T. Saari, J. C. Falcone, and D. A. Schuschke Neointima Formation in the Rat Carotid Artery Is Exacerbated by Dietary Copper Deficiency Experimental Biology and Medicine, July 1, 2002; 227(7): 487 - 491. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Kleschyov, M. Wendt, T. Munzel, D. A. Tulis, W. Durante, X. Liu, A. J. Evans, K. J. Peyton, and A. I. Schafer Heme Oxygenase-1-Mediated Protection: Potential Role of Nonheme Iron-Nitric Oxide Complexes * Response Circulation, June 25, 2002; 105 (25): e196 - e196. [Full Text] [PDF]
|
|
|
|
|
|
Y. Yuan, L. Liao, D. A. Tulis, and J. Xu Steroid Receptor Coactivator-3 Is Required for Inhibition of Neointima Formation by Estrogen Circulation, June 4, 2002; 105(22): 2653 - 2659. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Peyton, S. V. Reyna, G. B. Chapman, D. Ensenat, X.-m. Liu, H. Wang, A. I. Schafer, and W. Durante Heme oxygenase-1-derived carbon monoxide is an autocrine inhibitor of vascular smooth muscle cell growth Blood, May 29, 2002; 99(12): 4443 - 4448. [Abstract] [Full Text] [PDF]
|
|