title: Lanatoside C Promotes Foam Cell Formation and Atherosclerosis.
abstract: Lanatoside C's impact on atherosclerosis is poorly understood. The present study was conducted to determine whether lanatoside C affects the development of atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice. ApoE(-/-) mice were administered either phosphate-buffered saline (PBS) containing 0.1% DMSO (the vehicle control group) or lanatoside C at low (1 mg/kg per day) or high (2 mg/kg per day) doses, and fed a Western diet for 12 weeks. Lanatoside C dose-dependently aggravated the development of atherosclerosis in the ApoE(-/-) mice compared with the vehicle control group. In an effort to determine the mechanism by which lanatoside C increased atherosclerosis, we found that lanatoside C significantly promoted the uptake of oxidised low-density lipoprotein (oxLDL) and increased foam-cell formation by upregulation of scavenger receptor class A (SR-A) and the class B scavenger receptor (CD36) in macrophages. Meanwhile, the effects of lanatoside C were abolished using small interfering RNA (siRNA) inhibition of peroxisome proliferator-activated receptors β/δ (PPARβ/δ). Overall, our data demonstrate that lanatoside C aggravates the development of atherosclerosis by inducing PPARβ/δ expression, which mediates upregulation of SR-A and CD36, and promotes oxLDL uptake and foam-cell formation.
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Huairui
authors.initials: H
authors.lastname: Shi
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Mao
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yucheng
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yuzhou
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Kunwu
authors.initials: K
authors.lastname: Yu
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Zhu
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Wei
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jianghao
authors.initials: J
authors.lastname: Zhu
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Sun
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Mao
authors.affiliation: The Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Qiutang
authors.initials: Q
authors.lastname: Zeng
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D066273:Diet, Western / Q000009:adverse effects; D005487:Foam Cells / Q000378:metabolism* / Q000473:pathology; D007799:Lanatosides / Q000633:toxicity*; D017737:Macrophages, Peritoneal / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout
chemical_list: D001057:Apolipoproteins E; D007799:Lanatosides; C018548:lanatoside C
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