Tanshinone IIA suppresses cholesterol accumulation in human macrophages: Role of heme oxygenase-1

Liu, Zhiping, Wang, Jiaojiao, Huang, Erwen, Gao, Si, Li, Hong, Lu, Jing, Tian, Kunming, Little, Peter J., Shen, Xiaoyan, Xu, Suowen and Liu, Peiqing (2014) Tanshinone IIA suppresses cholesterol accumulation in human macrophages: Role of heme oxygenase-1. Journal of Lipid Research, 55 2: 201-213. doi:10.1194/jlr.M040394

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Author Liu, Zhiping
Wang, Jiaojiao
Huang, Erwen
Gao, Si
Li, Hong
Lu, Jing
Tian, Kunming
Little, Peter J.
Shen, Xiaoyan
Xu, Suowen
Liu, Peiqing
Title Tanshinone IIA suppresses cholesterol accumulation in human macrophages: Role of heme oxygenase-1
Journal name Journal of Lipid Research   Check publisher's open access policy
ISSN 0022-2275
Publication date 2014-01-01
Year available 2014
Sub-type Article (original research)
DOI 10.1194/jlr.M040394
Open Access Status File (Publisher version)
Volume 55
Issue 2
Start page 201
End page 213
Total pages 13
Place of publication Rockville, MD United States
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Abstract Accumulation of foam cells in the neointima represents a key event in atherosclerosis. We previously demonstrated that Tanshinone IIA (Tan), a lipophilic bioactive compound extracted from Salvia miltiorrhiza Bunge, inhibits experimental atherogenesis, yet the detailed mechanisms are not fully understood. In this study, we sought to explore the potential effects of Tan on lipid accumulation in macrophage foam cells and the underlying molecular mechanisms. Our data indicate that Tan treatment reduced the content of macrophages, cholesterol accumulation, and the development of atherosclerotic plaque in apolipoprotein E-deficient mice. In human macrophages, Tan ameliorated oxidized low density lipoporotein (oxLDL)-elicited foam cell formation by inhibiting oxLDL uptake and promoting cholesterol effl ux. Mechanistically, Tan markedly reduced the expression of scavenger receptor class A and increased the expression of ATP-binding cassette transporter A1 (ABCA1) and ABCG1 in lipid-laden macrophages via activation of the extracellular signal-regulated kinase (ERK)/nuclear factorerythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Tan treatment induced the phosphorylation and nuclear translocation of Nrf2 and subsequently increased the expression of HO-1, and these effects were abolished by the specific ERK inhibitors, PD98059 and U0126. Moreover, HO-1 small interfering RNA or zinc protoporphyrin (a HO-1 inhibitor) abrogated Tan-mediated suppression of lipid accumulation in macrophages. Our current findings demonstrate that a novel HO-1-dependent mechanism is involved in the regulation of cholesterol balance by Tan. -Liu, Z., J. Wang, E. Huang, S. Gao, H. Li, J. Lu, K. Tian, P. J. Little, X. Shen, S. Xu, and P. Liu. Tanshinone IIA suppresses cholesterol accumulation in human macrophages: role of heme oxygenase-1. Copyright
Keyword ATP binding cassette transporter A1/G1
Cell signaling
Class A scavenger receptor
Heme catabolism enzyme
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 81072641
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Pharmacy Publications
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Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
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