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Articles by C. C. Y Chang
Total Records ( 1 ) for C. C. Y Chang
  L Lei , Y Xiong , J Chen , J. B Yang , Y Wang , X. Y Yang , C. C. Y Chang , B. L Song , T. Y Chang and B. L. Li

High levels of the inflammatory cytokine tumor necrosis factor- (TNF-) are present in atherosclerotic lesions. TNF- regulates expression of multiple genes involved in various stages of atherosclerosis, and it exhibits proatherosclerotic and antiatherosclerotic properties. ACAT catalyzes the formation of cholesteryl esters (CE) in monocytes/macrophages, and it promotes the foam cell formation at the early stage of atherosclerosis. We hypothesize that TNF- may be involved in regulating the ACAT gene expression in monocytes/macrophages. In this article, we show that in cultured, differentiating human monocytes, TNF- enhances the expression of the ACAT1 but not ACAT2 gene, increases the cholesteryl ester accumulation, and promotes the lipid-laden cell formation. Several other proinflammatory cytokines tested do not affect the ACAT1 gene expression. The stimulation effect is consistent with a receptor-dependent process, and is blocked by using nuclear factor-kappa B (NF-kappa B) inhibitors. A functional and unique NF-kappa B element located within the human ACAT1 gene proximal promoter is required to mediate the action of TNF-. Our data demonstrate that TNF-, through the NF-kappa B pathway, specifically enhances the expression of human ACAT1 gene to promote the CE-laden cell formation from the differentiating monocytes, and our data support the hypothesis that TNF- is proatherosclerotic during early phase of lesion development.

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