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Adenovirus-Mediated Heme Oxygenase-1 Gene Delivery Inhibits Injury-Induced Vascular Neointima Formation
Abstract
BackgroundRecent 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 ResultsTwo 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. ConclusionsThese 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.
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Citations
Cited by
Different Faces of the Heme-Heme Oxygenase System in Inflammation
Wagener, F. A. D. T. G., Volk, H.-D., Willis, D., Abraham, N. G., Soares, M. P., Adema, G. J., & Figdor, C. G. (2003) · Pharmacological Reviews · doi:10.1124/pr.55.3.5 · Cited by 537
Heme Oxygenase-1: The “Emerging Molecule” Has Arrived
Morse, D., & Choi, A. M. K. (2002) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.27.1.4862 · Cited by 532
Heme oxygenase–1, oxidation, inflammation, and atherosclerosis
Araujo, J. A., Zhang, M., & Yin, F. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00119 · Cited by 443
Dysregulation of HSG triggers vascular proliferative disorders
Chen, K.-H., Guo, X., Ma, D., Guo, Y., Li, Q., Yang, D., Li, P., Qiu, X., Wen, S., Xiao, R.-P., et al. (2004) · Nature Cell Biology · doi:10.1038/ncb1161 · Cited by 370
Heme oxygenase and the cardiovascular–renal system
Abraham, N. G., & Kappas, A. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.03.010 · Cited by 356
Metadata
- Authors
- Tulis, D. A., Durante, W., Liu, X., Evans, A. J., Peyton, K. J., & Schafer, A. I.
- Venue
- Circulation
- Published
- 2001-11-27
- Volume
- 104
- Issue
- 22
- Pages
- 2710-2715
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2128304597
- Cited by
- 162
- References
- 0
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- closed
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- Tulis, D. A., Durante, W., Liu, X., Evans, A. J., Peyton, K. J., & Schafer, A. I. (2001). Adenovirus-Mediated Heme Oxygenase-1 Gene Delivery Inhibits Injury-Induced Vascular Neointima Formation. Circulation. https://doi.org/10.1161/hc4701.099585
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