1: Circulation. 2001 Nov 27;104(22):2710-5. 

Comment in:
    Circulation. 2002 Jun 25;105(25):e196; author reply e196.

Adenovirus-mediated heme oxygenase-1 gene delivery inhibits injury-induced
vascular neointima formation.

Tulis DA, Durante W, Liu X, Evans AJ, Peyton KJ, Schafer AI.

Departments of Medicine, Baylor College of Medicine, and Veterans Affairs
Medical Center, Houston, Texas, USA.

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.

PMID: 11723024 [PubMed - indexed for MEDLINE]