CTRP9 prevents atherosclerosis progression through changing autophagic status of macrophages by activating USP22 mediated-de-ubiquitination on Sirt1 in vitro.
Mol Cell Endocrinol
; 584: 112161, 2024 Apr 15.
Article
de En
| MEDLINE
| ID: mdl-38280475
ABSTRACT
BACKGROUND:
Atherosclerosis (AS) is commonly regarded as a key driver accounted for the leading causes of morbidity and mortality among cardiovascular and cerebrovascular diseases. A growing body of evidence indicates that autophagy in macrophages involved in AS might be a potential therapeutic target. C1q/TNF-related protein 9 (CTRP9) has been proven to delay the progression of cardiovascular diseases. However, the relations between CTRP9 and Sirt1, as well as their effects on macrophages autophagy have not been fully explored.METHODS:
Macrophages were differentiated from mononuclear cells collected from peripheral blood samples of healthy donors. The in vitro AS models were constructed by ox-LDL treatment. Cell viability was determined by CCK-8 assay. Immunofluorescence assay of LC3 was implemented for evaluating autophagy activity. Oil Red O staining was performed for lipid accumulation detection. ELISA, cholesterol concentration assay and cholesterol efflux analysis were conducted using commercial kits. Cycloheximide assay was implemented for revealing protein stability. RT-qPCR was used for mRNA expression detection, and western blotting was performed for protein level monitoring.RESULTS:
CTRP9 attenuated impaired cell viability, autophagy inhibition and increased lipid accumulation induced by ox-LDL. Moreover, CTRP9 maintained Sirt1 protein level through enhancing its stability through de-ubiquitination, which was mediated by upregulated USP22 level. CRTP9 exerted its protective role in promoting autophagy and reducing lipid accumulation through the USP22/Sirt1 axis.CONCLUSION:
Collectively, CTRP9 alleviates lipid accumulation and facilitated the macrophages autophagy by upregulating USP22 level and maintaining Sirt1 protein expression, thereby exerting a protective role in AS progression in vitro.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Athérosclérose
/
Sirtuine-1
Limites:
Humans
Langue:
En
Journal:
Mol Cell Endocrinol
Année:
2024
Type de document:
Article
Pays de publication:
Irlande