TY - JOUR
T1 - Reduced expression of heme oxygenase-1 in patients with coronary atherosclerosis
AU - Brydun, Andrei
AU - Watari, Yuichiro
AU - Yamamoto, Yoshiyuki
AU - Okuhara, Koichiro
AU - Teragawa, Hiroki
AU - Kono, Fujiko
AU - Chayama, Kazuaki
AU - Oshima, Tetsuya
AU - Ozono, Ryoji
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/4
Y1 - 2007/4
N2 - 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/I 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.
AB - 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/I 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.
KW - Atherosclerosis
KW - Hemoxygenase-1 gene expression
KW - Oxidative stress
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U2 - 10.1291/hypres.30.341
DO - 10.1291/hypres.30.341
M3 - Article
C2 - 17541213
AN - SCOPUS:34249062039
VL - 30
SP - 341
EP - 348
JO - Hypertension Research
JF - Hypertension Research
SN - 0916-9636
IS - 4
ER -
