Haem oxygenase-1 inhibits neointimal hyperplasia in rat by histone deacetylase 2.

It has been reported that haem oxygenase-1 (Hmox1) induction attenuates neointimal thickening. Here we further investigated the potential mechanisms regulating this important pathological process. We revealed that histone deacetylase 2 (HDAC2) was induced following Hmox1 induction under 1% oxygen treatment and this induction was attenuated after the treatment of siRNA against Hmox1. Interestingly, this HDAC2 induction was dependent on Hmox1 protein as well as its enzymatic activity, and was regulated by carbon monoxide released from haem degradation. Furthermore, histone deacetylase inhibitor, trichostatin A, successfully abrogated the inhibitory effects of vascular smooth muscle migration and proliferation by Hmox1 induction in vitro. In a rat carotid balloon injury model, similar results were observed by measuring neointimal thickening. As such, we concluded that Hmox1 inhibits neointimal hyperplasia via HDAC2 in rats.