Heme oxigenase-1 (HO-1) is known to be an inducible cytoprotective enzyme that copes with oxidative stress. However, changes in HO-1 expression and their association with human diseases have not been studied. To test the hypothesis that the capacity to upregulate HO-1 in response to oxidative stress is an intrinsic marker for susceptibility to coronary atherosclerosis, we assessed stimulation-induced change in HO-1 expression in blood cells in 110 patients who underwent coronary angiography, comparing the results with the extent of coronary atherosclerosis and (GT)n repeat polymorphism in the HO-1 gene promoter region, which is believed to affect the gene expression level. The extent of coronary atherosclerosis was assessed by coronary score. Mononuclear cells were incubated with 10 μmol/l hemin or vehicle for 4 h to maximally stimulate HO-1 expression, then the HO-1 expression level was determined by real-time polymerase chain reaction (PCR). The difference between the HO-1 mRNA levels of hemin- and vehicle-treated cells (ΔHO-1 mRNA) was taken as an index of the capacity to upregulate HO-1 mRNA. The coefficient of variance of ΔHO-1 mRNA was 7.2%. Consistent with previous studies, ΔHO-1 mRNA was significantly lower in patients carrying a long (GT)n repeat. ΔHO-1 mRNA negatively and significantly correlated with the coronary score (r2=0.50, p<0.01). In conclusion, the capacity to upregulate HO-1 expression may be determined, at least in part, by genetics, and reduced ability to induce HO-1 may be involved in the mechanism of coronary atherosclerosis.
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Brydun, A., Watari, Y., Yamamoto, Y. et al. Reduced Expression of Heme Oxygenase-1 in Patients with Coronary Atherosclerosis. Hypertens Res 30, 341–348 (2007). https://doi.org/10.1291/hypres.30.341
- hemoxygenase-1 gene expression
- oxidative stress
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