Increased ferritin gene expression in atherosclerotic lesions.
To identify genes potentially implicated in atherogenesis, a cDNA library was constructed from human atherosclerotic aorta and differentially screened with 32P-labeled-cDNAs prepared from human normal and atherosclerotic aortas. Two cDNA clones exhibiting higher hybridization to the 32P-labeled cDNAs from atherosclerotic vessels were isolated and identified to be genes encoding L-ferritin and H-ferritin, respectively. Northern blot analysis confirmed that the expression of both ferritin genes was notably higher in human and rabbit atherosclerotic aortas than in their normal counterparts. A time-course study illustrated that both L- and H-ferritin mRNAs were markedly increased in aortas of rabbits after feeding with a high cholesterol diet for 6 wk, which was also the time period after which the formation of lesions became evident. In situ hybridization revealed that both L- and H-ferritin mRNAs were induced in endothelial cells and macrophages of human early lesions. The signals were also detected in the smooth muscle cells of advanced lesions. Immunostaining further identified the presence of ferritin protein in atherosclerotic lesions. On the other hand, Prussian blue stain revealed the presence of iron deposits in advanced lesions but not in early human or rabbit lesions. Further experiments with cultured human monocytic THP-1 cells and aortic smooth muscle cells demonstrated that ferritin mRNAs were subjected to up-regulation by treatment with IL-1 or TNF, while TGF, PDGF, and oxidized LDL did not affect the expression of either ferritin gene in both cell lines. Collectively, these results clearly demonstrate that ferritin genes are susceptible to induction in the course of plaque formation.
Pang
J H
JH
Division of Cardiovascular Research, Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei, Republic of China.
Jiang
M J
MJ
Chen
Y L
YL
Wang
F W
FW
Wang
D L
DL
Chu
S H
SH
Chau
L Y
LY
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000032:analysis; D005293:Ferritins / Q000032:analysis / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000494:pharmacology; D007501:Iron / Q000032:analysis; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism; D010084:Oxidation-Reduction; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018076:DNA, Complementary; D007375:Interleukin-1; D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; D005293:Ferritins; D007501:Iron