1: Circulation. 2002 Jan 1;105(1):79-84. 

Adenovirus-mediated heme oxygenase-1 gene expression stimulates apoptosis in
vascular smooth muscle cells.

Liu XM, Chapman GB, Wang H, Durante W.

Houston VA Medical Center and the Department of Medicine, Baylor College of
Medicine, Houston, Tex 77030, USA.

BACKGROUND: Heme oxygenase-1 (HO-1) catalyzes the degradation of heme into
biliverdin, iron, and carbon monoxide (CO). Although HO-1 is induced in vascular
smooth muscle cells (SMCs), the biological role of HO-1 in these cells has not
been completely characterized. METHODS AND RESULTS: In the present study, we
overexpressed HO-1 in rat aortic SMCs by generating a recombinant defective
adenovirus containing the rat HO-1 gene (AdHO-1) and examined the effect on SMC
proliferation. Infection of SMCs with AdHO-1 resulted in a dose-dependent
increase in the expression of HO-1 mRNA, protein, and activity. Infection of
SMCs with AdHO-1 inhibited serum-stimulated SMC proliferation in a
dose-dependent manner. In contrast, the control adenovirus expressing the green
fluorescent protein failed to induce HO-1 expression and had minimal effects on
SMC growth. Infection with AdHO-1 stimulated SMC apoptosis in a dose-dependent
fashion, as demonstrated by DNA fragmentation, positive annexin V labeling, and
caspase-3 activation. HO-1-mediated apoptosis was associated with a marked
increase in the expression of the proapoptotic protein p53. Finally, the
exogenous administration of biliverdin and bilirubin stimulated SMC apoptosis.
In contrast, the administration of CO or iron failed to induce cell death.
CONCLUSIONS: These results demonstrate that overexpression of HO-1 or the
exogenous administration of biliverdin or bilirubin stimulates SMC apoptosis.
Adenovirus-mediated transfer of the HO-1 gene may provide a novel therapeutic
approach in treating occlusive vascular disease.

PMID: 11772880 [PubMed - indexed for MEDLINE]