Disulfiram protects against abdominal aortic aneurysm by ameliorating vascular smooth muscle cells pyroptosis.
Cardiovasc Drugs Ther
; 37(6): 1-14, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-35723784
ABSTRACT
PURPOSE:
Recent studies demonstrated that pyroptosis is involved in abdominal aortic aneurysm (AAA) progression, suggesting a potential target for AAA treatment. This study aimed to identify if disulfiram could inhibit angiotensin II (Ang II)-induced vascular smooth muscle cells (VSMCs) damage, thereby exerting protective effects on AAA.METHODS:
The AAA mouse model was established by continuous subcutaneous Ang II infusion for 28 days. Then aortic tissue of the mice was isolated and subjected to RNA sequencing, qRT-PCR, Western blotting, and immunofluorescence staining. To explore the therapeutic effect of disulfiram, mice were orally administered disulfiram (50 mg/kg/day) or vehicle for 28 days accompanied with Ang II infusion. Pathological changes in aortic tissues were measured using microultrasound imaging analysis and histopathological analysis. In addition, inflammatory response, pyroptosis, and oxidative stress damage were examined in mouse aortic vascular smooth muscle (MOVAS) cells stimulated with Ang II in vitro.RESULTS:
The RNA sequencing and bioinformatic analysis results suggested that pyroptosis- and inflammation-related genes were significantly upregulated in AAA, consistent with the results of qRT-PCR and Western blotting. Most importantly, the therapeutic effect of disulfiram on AAA was identified in our study. First, disulfiram administration significantly attenuated Ang II-induced inflammation, pyroptosis, and oxidative stress in VSMCs, which is associated with the inhibition of the NF-κB-NLRP3 pathway. Second, in-vivo studies revealed that disulfiram treatment reduced AAA formation and significantly ameliorated collagen deposition and elastin degradation in the aortic wall.CONCLUSION:
Our findings suggest that disulfiram has a novel protective effect against AAA by inhibiting Ang II-induced VSMCs pyroptosis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aneurisma da Aorta Abdominal
/
Músculo Liso Vascular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cardiovasc Drugs Ther
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China