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.
