Trichostatin A exacerbates atherosclerosis in low density lipoprotein receptor-deficient mice

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Trichostatin A exacerbates atherosclerosis in low density lipoprotein receptor-deficient mice
J H Choi; Ki Hoan Nam; JiYun Kim; M W Baek; J E Park; H Y Park; H J Kwon; O S Kwon; D Y Kim; G T Oh
Bibliographic Citation
Arteriosclerosis Thrombosis and Vascular Biology, vol. 25, no. 11, pp. 2404-2409
Publication Year
Objective - Histone acetylation has been shown to be involved in expression of a restricted set of cellular genes including various proinflammatory molecules. We aimed to investigate the relationship between histone acetylation and atherosclerosis. Methods and Results - In low-density lipoprotein (LDL) receptor-deficient (Ldlr-/-) mice fed an atherogenic diet for 4 or 8 weeks, trichostatin A (TSA), a specific histone deacetylase inhibitor, exacerbated atherosclerosis without alteration on plasma lipid profiles. When we assayed the effects of TSA on expressions of oxidized LDL (oxLDL) receptors on RAW264.7 macrophage, we found that TSA increased CD36 mRNA and protein, as well as cell surface expression of CD36. TSA also increased acetylation at the CD36 promoter region. The uptake of l,l′-dioctadecyl-3,3,3′,3′- tetramethylindocarbocyanine percholate (Dil)-labeled oxLDL was enhanced in RAW264.7 macrophage by TSA. Furthermore, TSA treatment increased CD36 mRNA expression in aorta, and SRA, tumor necrosis factor (TNF)-α, and vascular cell adhesion molecule-1 (VCAM-1) were also elevated, whereas IL-6 and IL-1β expressions were decreased. Conclusions - Our findings suggest that histone acetylation could play some role in atherogenesis by modulating expressions of oxLDL receptor and some proatherogenic genes. Therefore, our results indicate that increased histone acetylation may affect the progress of atherosclerosis.
atherosclerosishistone acetylationescavenger receptorstrichostatin A
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Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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