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Tanshinone IIA Promotes Macrophage Cholesterol Efflux and Attenuates Atherosclerosis of apoE-/- Mice by Omentin-1/ABCA1 Pathway

[ Vol. 20 , Issue. 5 ]

Author(s):

Yu-lin Tan, Han-xiao Ou, Min Zhang, Duo Gong, Zhen-wang Zhao, Ling-yan Chen, Xiao-dan Xia, Zhong-cheng Mo* and Chao-ke Tang*   Pages 422 - 432 ( 11 )

Abstract:


Background: Tanshinone IIA (Tan IIA) and Omentin-1 have a protective role in the cardiovascular system. However, if and how Tan IIA and Omentin-1 regulate cholesterol metabolism in macrophages has not been fully elucidated.

Objective: To investigate the possible mechanisms of Tan IIA and Omentin-1 on preventing macrophage cholesterol accumulation and atherosclerosis development.

Methods: The effect of Tan IIA on the protein and mRNA levels of Omentin-1 and ATP-binding cassette transporter A1 (ABCA1) in macrophages was examined by Western blot and qRT-PCR assay, respectively. Cholesterol efflux was assessed by liquid scintillation counting (LSC). Cellular lipid droplet was measured by Oil Red O staining, and intracellular lipid content was detected by high performance liquid chromatography (HPLC). In addition, the serum lipid profile of apoE−/− mice was measured by an enzymatic method. The size of atherosclerotic lesion areas and content of lipids and collagen in the aortic of apoE−/− mice were examined by sudan IV, Oil-red O, and Masson staining, respectively.

Results: Tan IIA up-regulated expression of Omentin-1 and ABCA1 in THP-1 macrophages, promoting ABCA1-mediated cholesterol efflux and consequently decreasing cellular lipid content. Consistently, Tan IIA increased reverse cholesterol transport in apoE−/− mice. Plasma levels of high-density lipoprotein cholesterol (HDL-C), ABCA1 expression and atherosclerotic plaque collagen content were increased while plasma levels of low-density lipoprotein cholesterol (LDL-C) and atherosclerotic plaque sizes were reduced in Tan IIA-treated apoE−/− mice. These beneficial effects were, however, essentially blocked by knockdown of Omentin-1.

Conclusions: Our results revealed that Tan IIA promotes cholesterol efflux and ameliorates lipid accumulation in macrophages most likely via the Omentin-1/ABCA1pathway, reducing the development of aortic atherosclerosis.

Keywords:

Tan IIA, Omentin-1, ABCA1, cholesterol efflux, reverse cholesterol transport, plaque vulnerability.

Affiliation:

Institute of Cardiovascular disease, Key Laboratory for Arterosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, Cooperative Innovation Base of Basic and Clinic Medicine, University of South China & Yueyan Maternity-Child Health Hospital, Department of genetics and eugenics, Yueyan Maternity-Child Health Hospital, 414000, Hunan, Institute of Cardiovascular disease, Key Laboratory for Arterosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, Institute of Cardiovascular disease, Key Laboratory for Arterosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, Institute of Cardiovascular disease, Key Laboratory for Arterosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, Institute of Cardiovascular disease, Key Laboratory for Arterosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, Institute of Cardiovascular disease, Key Laboratory for Arterosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan, Cooperative Innovation Base of Basic and Clinic Medicine, University of South China & Yueyan Maternity-Child Health Hospital, Department of genetics and eugenics, Yueyan Maternity-Child Health Hospital, 414000, Hunan, Institute of Cardiovascular disease, Key Laboratory for Arterosclerology of Hunan Province, Medical Research Center, Hunan Province Cooperative innovation Center for Molecular Target New Drug Study, University of South China, Hengyang 421001, Hunan



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