Niclosamide downregulates LOX-1 expression in mouse vascular smooth muscle cells and changes the composition of atherosclerotic plaques in ApoE−/− mice View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2021-11-22

AUTHORS

Tao Yang, Manabu Minami, Kazumichi Yoshida, Manabu Nagata, Yu Yamamoto, Naoki Takayama, Keita Suzuki, Takeshi Miyata, Masakazu Okawa, Susumu Miyamoto

ABSTRACT

Genetic lineage tracing studies have shown that phenotypic switching of vascular smooth muscle cells (VSMCs) results in less-differentiated cells, including macrophage-like cells that lack traditional VSMC markers. This switching contributes to the formation of necrotic core in plaques and promotes atherosclerosis, which is important for plaque stability. Niclosamide, a commonly used anti-helminthic drug, has recently attracted attention as an anti-cancer drug that inhibits multiple signaling pathways. The expression of the S100A4 protein is upregulated in synthetic VSMCs and inhibited by niclosamide on metastatic progression in colon cancer. We aimed to test the effect of niclosamide on VSMC phenotype switching and plaque stability. To examine murine atherosclerosis, we induced experimental lesions by blood flow cessation in apolipoprotein E knockout mice fed a high-fat diet. Oral administration of niclosamide changed 4-week-old plaques to collagen-rich and less-necrotic core phenotypes and downregulated the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in vivo. In vitro analysis indicated that niclosamide reduced LOX-1 expression in VSMCs in a concentration-dependent and S100A4-independent manner. The inhibitory effect of niclosamide on LOX-1 and collagen type I was associated with the inactivation of the nuclear factor-κB signaling pathway. We demonstrated that the administration of niclosamide reduced LOX-1 expression and altered the composition of murine carotid plaques. Our results highlight the potential of niclosamide as an atheroprotective agent that enhances atherosclerotic plaque stability. More... »

PAGES

517-527

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00380-021-01983-z

DOI

http://dx.doi.org/10.1007/s00380-021-01983-z

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/34807278


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85 muscle cells
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87 niclosamide
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89 oxidized low-density lipoprotein receptor-1
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94 plaque stability
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