Medium-Dose Formoterol Attenuated Abdominal Aortic Aneurysm Induced by EPO via ß2AR/cAMP/SIRT1 Pathway.
Adv Sci (Weinh)
; 11(15): e2306232, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38353392
ABSTRACT
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease but effective drugs for treatment of AAA are still lacking. Recently, erythropoietin (EPO) is reported to induce AAA formation in apolipoprotein-E knock out (ApoE-/-) mice but an effective antagonist is unknown. In this study, formoterol, a ß2 adrenergic receptor (ß2AR) agonist, is found to be a promising agent for inhibiting AAA. To test this hypothesis, ApoE-/- mice are treated with vehicle, EPO, and EPO plus low-, medium-, and high-dose formoterol, respectively. The incidence of AAA is 0, 55%, 35%,10%, and 55% in these 5 groups, respectively. Mechanistically, senescence of vascular smooth muscle cell (VSMC) is increased by EPO while decreased by medium-dose formoterol both in vivo and in vitro, manifested by the altered expression of senescence biomarkers including phosphorylation of H2AXserine139, senescence-associated ß-galactosidase activity, and P21 protein level. In addition, expression of sirtuin 1 (SIRT1) in aorta is decreased in EPO-induced AAA but remarkably elevated by medium-dose formoterol. Knockdown of ß2AR and blockage of cyclic adenosine monophosphate (cAMP) attenuate the inhibitory role of formoterol in EPO-induced VSMC senescence. In summary, medium-dose formoterol attenuates EPO-induced AAA via ß2AR/cAMP/SIRT1 pathways, which provides a promising medication for the treatment of AAA.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Eritropoetina
/
Aneurisma da Aorta Abdominal
/
Fumarato de Formoterol
Limite:
Animals
Idioma:
En
Revista:
Adv Sci (Weinh)
Ano de publicação:
2024
Tipo de documento:
Article