Formononetin attenuates atherosclerosis via regulating interaction between KLF4 and SRA in apoE-/- mice Article Swipe
Chuanrui Ma
,
Ronglin Xia
,
Shu Yang
,
Lipei Liu
,
Jing Zhang
,
Ke Feng
,
Yuna Shang
,
Jingtian Qu
,
Lingwei Li
,
Ning Chen
,
Shixin Xu
,
Wenwen Zhang
,
Jingyuan Mao
,
Jihong Han
,
Yuanli Chen
,
Xiaoxiao Yang
,
Yajun Duan
,
Guanwei Fan
·
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.7150/thno.38115
YOU?
·
· 2019
· Open Access
·
· DOI: https://doi.org/10.7150/thno.38115
Background and Purpose: Atherosclerosis is an underlying cause of coronary heart disease. Foam cell, a hallmark of atherosclerosis, is prominently derived from monocyte-differentiated macrophage, and vascular smooth muscle cells (VSMCs) through unlimitedly phagocytizing oxidized low-density lipoprotein (oxLDL). Therefore, the inhibition of monocyte adhesion to endothelium and uptake of oxLDL might be a breakthrough point for retarding atherosclerosis. Formononetin, an isoflavone extracted from Astragalus membranaceus, has exhibited multiple inhibitory effects on proatherogenic factors, such as obesity, dyslipidemia, and inflammation in different animal models. However, its effect on atherosclerosis remains unknown. In this study, we determined if formononetin can inhibit atherosclerosis and elucidated the underlying molecular mechanisms. Methods: ApoE deficient mice were treated with formononetin contained in high-fat diet for 16 weeks. After treatment, mouse aorta, macrophage and serum samples were collected to determine lesions, immune cell profile, lipid profile and expression of related molecules. Concurrently, we investigated the effect of formononetin on monocyte adhesion, foam cell formation, endothelial activation, and macrophage polarization in vitro and in vivo. Results: Formononetin reduced en face and aortic root sinus lesions size. Formononetin enhanced lesion stability by changing the composition of plaque. VSMC- and macrophage-derived foam cell formation and its accumulation in arterial wall were attenuated by formononetin, which might be attributed to decreased SRA expression and reduced monocyte adhesion. Formononetin inhibited atherogenic monocyte adhesion and inflammation. KLF4 negatively regulated the expression of SRA at transcriptional and translational level. Conclusions: Our study demonstrate that formononetin can substantially attenuate the development of atherosclerosis via regulation of interplay between KLF4 and SRA, which suggests the formononetin might be a novel therapeutic approach for inhibition of atherosclerosis.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.7150/thno.38115
- OA Status
- gold
- Cited By
- 124
- References
- 69
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2993607665
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2993607665Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.7150/thno.38115Digital Object Identifier
- Title
-
Formononetin attenuates atherosclerosis via regulating interaction between KLF4 and SRA in apoE-/- miceWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2019Year of publication
- Publication date
-
2019-12-06Full publication date if available
- Authors
-
Chuanrui Ma, Ronglin Xia, Shu Yang, Lipei Liu, Jing Zhang, Ke Feng, Yuna Shang, Jingtian Qu, Lingwei Li, Ning Chen, Shixin Xu, Wenwen Zhang, Jingyuan Mao, Jihong Han, Yuanli Chen, Xiaoxiao Yang, Yajun Duan, Guanwei FanList of authors in order
- Landing page
-
https://doi.org/10.7150/thno.38115Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.7150/thno.38115Direct OA link when available
- Concepts
-
Formononetin, Inflammation, Monocyte, Chemistry, Foam cell, Cell adhesion molecule, Cell adhesion, Macrophage, Endocrinology, Internal medicine, Immunology, Cell, Biochemistry, Medicine, In vitro, Daidzein, GenisteinTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
124Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 30, 2024: 32, 2023: 23, 2022: 14, 2021: 19Per-year citation counts (last 5 years)
- References (count)
-
69Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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