Recombinant Klotho protein enhances cholesterol efflux of THP-1 macrophage-derived foam cells via suppressing Wnt/ß-catenin signaling pathway.
BMC Cardiovasc Disord
; 20(1): 120, 2020 03 05.
Article
em En
| MEDLINE
| ID: mdl-32138681
ABSTRACT
BACKGROUND:
Atherosclerosis (AS) is the basis of cardiovascular diseases, characterized by chronic inflammatory and lipid metabolism disorders. Although the anti-inflammatory effect of Klotho in AS has been clearly shown, its lipid-lowering effect is unclear. In this study, we examined the effects of recombinant Klotho (Re-KL) protein on lipid accumulation in foam cells.METHODS:
THP-1 cells were exposed to 100 nM phorbol myristate acetate for 24 h and then to oxidized low-density lipoprotein (ox-LDL; 80 mg/mL) to induce foam cell formation. Subsequently, the foam cells were incubated with Re-KL and/or DKK1, an inhibitor of the Wnt/ß-catenin pathway.RESULTS:
Oil red O staining and cholesterol intake assay revealed that the foam cell model was constructed successfully. Pre-treatment of the foam cells with Re-KL decreased total cholesterol level, up-regulated the expression of ATP binding cassette transporter A1 (ABCA1) and G1 (ABCG1), and down-regulated the expression of acyl coenzyme a-cholesterol acyltransferase 1 (ACAT1) and members of the scavenger family (SR-A1 and CD36). In addition, the expression of Wnt/ß-catenin pathway-related proteins in foam cells was significantly decreased by the stimulus of Re-KL. Interestingly, the effect of Re-KL was similar to that of DKK1 on foam cells.CONCLUSIONS:
The Re-KL-induced up-regulation of reverse cholesterol transport capacity promotes cholesterol efflux and reduces lipid accumulation by suppressing the Wnt/ß-catenin pathway in foam cells.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Colesterol
/
Metabolismo dos Lipídeos
/
Via de Sinalização Wnt
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Células Espumosas
/
Glucuronidase
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Anticolesterolemiantes
Limite:
Humans
Idioma:
En
Revista:
BMC Cardiovasc Disord
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China