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
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