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

Jae Hoon Choi, Ki Hoan Nam, Jiyun Kim, Min Won Baek, Jeong Euy Park, Hyun Young Park, Ho Jeong Kwon, Oh Seung Kwon, Dae Yong Kim, Goo Taeg Oh

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2404-2409
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume25
Issue number11
DOIs
Publication statusPublished - 2005 Nov 1

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Choi, J. H., Nam, K. H., Kim, J., Baek, M. W., Park, J. E., Park, H. Y., Kwon, H. J., Kwon, O. S., Kim, D. Y., & Oh, G. T. (2005). Trichostatin A exacerbates atherosclerosis in low density lipoprotein receptor-deficient mice. Arteriosclerosis, thrombosis, and vascular biology, 25(11), 2404-2409. https://doi.org/10.1161/01.ATV.0000184758.07257.88