Effect of hypoxia on the expression of HO-1 mRNA and the proliferation of pulmonary arterial smooth muscle cells in rats

To explore the expression of the HO 1mRNA in pulmonary arterial vascular smooth muscle cell (PASMC) and the heme oxygenase 1/carbon monoxide (HO 1/CO) system on PASMC proliferation in hypoxic rats. HO 1 mRNA in cultured PASMC was measured by fluorescent quantitative RT PCR. The carbon monoxide hemoglobin(HbCO)was quantitated with spectrophotometry. Suggestion of PASMC proliferation status were performed using immunocytochemistry of PCNA and NF κB. We found that the expression of HO 1 mRNA of PASMC was in low basal level under mornoxia ,after hypoxic treatment for 12 hours, the amount of HO 1 mRNA in PASMC increased by 50% associated with a significant increase of HbCO level ( P 0.01, as compared to those of normoxic controls). After hypoxic treatment for 24 hours, however, the content of HO 1 mRNA and HbCO in PASMC reduced, though they were still higher than those of normoxic controls. After hypoxic treatment for 12 or 24 hours, immuno positive signals of PCNA on PASMC increased significantly ( P 0.01 and 0.001, respectively, as compared to those of control group). When zinc protoporphyrin (ZnPP), a heme oxygenase inhibitor, was used in combination with hypoxia to treat PASMC for 12 or 24 hours, immuno positive signals of PCNA increased further ( P 0.001 and 0.01, respectively, as compared with those of groups treated with hypoxia but without ZnPP). The immunocytochemistry change of NF κB in PASMC was in parallel with those of PCNA. Hypoxia induces PASMC to raise the level of HO 1 mRNA and upregulates the activity of HO 1 / CO system, resulting in the increase of endogenous CO and thus the inhibition of PASMC proliferation. NF κB may also be involved in the regulation of PASMC proliferation.