EXPRESSION OF HEME OXYGENASE-1 IN ATHEROSCLEROTIC LESIONS

Heme oxygenase-1 (HO-1) is a heme-degradation enzyme induced under var ious oxidative stress conditions. To elucidate the potential involveme nt of HO-1 in atherogenesis, the expression of this enzyme in atherosc lerotic lesions of apolipoprotein E-deficient mice and humans were exa mined. Both immunostaining and in situ hybridization clearly demonstra ted that the expression of HO-1 was prominent in endothelium and foam cells/macrophages of thickened intima in lesions from both humans and experimental animals. The expression of this enzyme was also detected in medial smooth muscle cells of advanced lesions. The induction of HO -1 mRNA was observed in murine peritoneal macrophages after treatment with oxidized low density lipoprotein (LDL) but not with native LDL in a dose-dependent manner. Time course study demonstrated that the indu ction was prominent at 3 hours, reached a maximal induction at 6 hours , and remained evident up to 24 hours after oxidized LDL treatment. Th e degree of induction was in concordant with the extent of oxidation i n the LDL preparation. Lysophosphatidylcholine, one of the major compo nents present in oxidized LDL, was Ineffective to induce the gene expr ession, suggesting that other lipophilic substances derived from LDL o xidation are responsible for the induction of HO-1. These results clea rly demonstrate that HO-1 is one of the stress proteins expressed in a therosclerotic lesions.