Expression of heme oxygenase-1 in atherosclerotic lesions.
Heme oxygenase-1 (HO-1) is a heme-degradation enzyme induced under various oxidative stress conditions. To elucidate the potential involvement of HO-1 in atherogenesis, the expression of this enzyme in atherosclerotic lesions of apolipoprotein E-deficient mice and humans were examined. Both immunostaining and in situ hybridization clearly demonstrated 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 induction was prominent at 3 hours, reached a maximal induction at 6 hours, and remained evident up to 24 hours after oxidized LDL treatment. The degree of induction was in concordant with the extent of oxidation in the LDL preparation. Lysophosphatidylcholine, one of the major components present in oxidized LDL, was ineffective to induce the gene expression, suggesting that other lipophilic substances derived from LDL oxidation are responsible for the induction of HO-1. These results clearly demonstrate that HO-1 is one of the stress proteins expressed in atherosclerotic lesions.
Wang
L J
LJ
Division of Cardiovascular Research, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
Lee
T S
TS
Lee
F Y
FY
Pai
R C
RC
Chau
L Y
LY
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001011:Aorta / Q000201:enzymology* / Q000473:pathology; D001161:Arteriosclerosis / Q000201:enzymology* / Q000473:pathology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008077:Lipoproteins, LDL / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism
D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D012333:RNA, Messenger; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse