Heme oxygenase-1 (HO-1) alleviates vascular restenosis after balloon injury in a rabbit carotid artery model.

Percutaneous coronary intervention (PCI) is used commonly for coronary artery disease (CAD); however, restenosis is a proliferative response and frequent sequela to this treatment. Although the introduction of drug-eluting stents has convincingly reduced the incidence of vascular restenosis, restenosis remains a problem. The present study was designed to investigate the effects of the heme oxygenase-1 (HO-1) on restenosis formation after balloon injury in a rabbit carotid artery model. We found that involvement of the HO-1 in defensive restenosis formation was independent of the levels of blood lipid. Activation of HO-1 induced by chlorhematin treatment alleviated vascular restenosis after balloon injury in a rabbit carotid artery model, whereas inhibition of HO-1 by zinc protoporphyrin treatment exacerbated restenosis formation. Furthermore, overexpression of HO-1 inhibited nuclear factor kappa B subunit 1 (NF-кB) activity and decreased tumor necrosis factor-alpha (TNF-α) and endothelin 1 (ET-1) expression. In conclusion, our study provides preliminary data suggesting that HO-1 alleviates vascular restenosis after balloon injury in a rabbit carotid artery model by inhibiting NF-кB, TNF-α and ET-1 expression, indicating induction of HO-1 activation may be a feasible therapeutic target for treating vessels resistant to restenosis.