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Abstract Title:

Tanshinone IIA promotes macrophage cholesterol efflux and attenuates atherosclerosis of apoE-/- mice by Omentin-1/ABCA1 pathway.

Abstract Source:

Curr Pharm Biotechnol. 2019 Apr 4. Epub 2019 Apr 4. PMID: 30947667

Abstract 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

Article Affiliation:

Yu-Lin Tan

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.

Study Type : Animal Study

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