Rutaecarpine suppresses atherosclerosis in ApoE-/- mice through upregulating ABCA1 and SR-BI within RCT.

Abstract

ABCA1 and scavenger receptor class B type I (SR-BI)/CD36 and lysosomal integral membrane protein II analogous 1 (CLA-1) are the key transporter and receptor in reverse cholesterol transport (RCT). Increasing the expression level of ABCA1 and SR-BI/CLA-1 is antiatherogenic. The aim of the study was to find novel antiatherosclerotic agents upregulating expression of ABCA1 and SR-BI/CLA-1 from natural compounds. Using the ABCA1p-LUC and CLA-1p-LUC HepG2 cell lines, we found that rutaecarpine (RUT) triggered promoters of ABCA1 and CLA-1 genes. RUT increased ABCA1 and SR-BI/CLA-1 expression in vitro related to liver X receptor alpha and liver X receptor beta. RUT induced cholesterol efflux in RAW264.7 cells. ApoE-deficient (ApoE(-/-)) mice treated with RUT for 8 weeks showed ∼68.43, 70.23, and 85.56% less en face lesions for RUT (L), RUT (M), and RUT (H) groups, respectively, compared with the model group. Mouse macrophage-specific antibody and filipin staining indicated that RUT attenuated macrophages and cholesterol accumulations in atherosclerotic lesions, respectively. Additionally, ABCA1 and SR-BI expression was highly induced by RUT in livers of ApoE(-/-) mice. Meanwhile, RUT treatment significantly increased the fecal (3)H-cholesterol excretion, which demonstrated that RUT could promote RCT in vivo. RUT was identified to be a candidate that protected ApoE(-/-) mice from developing atherosclerosis through preferentially promoting activities of ABCA1 and SR-BI within RCT.

• Authors: Yanni Xu, Qi Liu, Yang Xu, Chang Liu, Xiao Wang, Xiaobo He, Ningyu Zhu, Jikai Liu, Yexiang Wu, Yongzhen Li, Ni Li, Tingting Feng, Fangfang Lai, Murui Zhang, Bin Hong, Jian-Dong Jiang, Shuyi Si
• Journal: Journal of lipid research (J Lipid Res) Vol. 55 Issue 8 Pg. 1634-47 (Aug 2014) ISSN: 1539-7262 [Electronic] United States
• PMID: 24908654 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• ABCA1 protein, human
• ABCA1 protein, mouse
• ATP Binding Cassette Transporter 1
• Apolipoproteins E
• Indole Alkaloids
• Quinazolines
• SCARB1 protein, human
• Scarb1 protein, mouse
• Scavenger Receptors, Class B
• rutecarpine

Topics

• ATP Binding Cassette Transporter 1 (biosynthesis, genetics)
• Animals
• Apolipoproteins E (genetics, metabolism)
• Atherosclerosis (genetics, metabolism, pathology, prevention & control)
• Indole Alkaloids (pharmacology)
• Liver (metabolism, pathology)
• Mice
• Mice, Knockout
• Quinazolines (pharmacology)
• RAW 264.7 Cells
• Scavenger Receptors, Class B (genetics, metabolism)