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

Author(s): Yu-lin Tan , Han-xiao Ou , Min Zhang , Duo Gong , Zhen-wang Zhao , Ling-yan Chen , Xiao-dan Xia , Zhong-cheng Mo* , Chao-ke Tang* .

Journal Name: Current Pharmaceutical Biotechnology

Volume 20 , Issue 5 , 2019

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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 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.

Conclusion: Our results revealed that Tan IIA promotes cholesterol efflux and ameliorates lipid accumulation in macrophages most likely via the Omentin-1/ABCA1 pathway, reducing the development of aortic atherosclerosis.

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

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Article Details

VOLUME: 20
ISSUE: 5
Year: 2019
Page: [422 - 432]
Pages: 11
DOI: 10.2174/1389201020666190404125213
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