Hyperuricemia exacerbates abdominal aortic aneurysm formation through the URAT1/ERK/MMP-9 signaling pathway.
BMC Cardiovasc Disord
; 23(1): 55, 2023 01 30.
Article
em En
| MEDLINE
| ID: mdl-36710339
ABSTRACT
OBJECTIVE:
Previous studies have revealed associations between hyperuricemia and microvascular diseases, but the association between hyperuricemia and abdominal aortic aneurysm (AAA) remains unclear. The aim of this study was to elucidate the pathogenesis and prove the relationship between AAA and hyperuricemia.METHODS:
A retrospective study was performed to validate the growth rates of AAA in humans with different serum uric acid levels. A murine model of angiotensin II-induced AAA was used to assess the effects of hyperuricemia on AAA growth in vivo, and human aortic smooth muscle cells (HASMCs) were used to study the pathways involved in these effects in vitro.RESULTS:
We analyzed data from 107 AAA patients and found that patients with serum uric acid levels above 9 mg/dl had higher AAA growth rates than patients with serum uric acid levels between 4 and 7.9 mg/dl. In vivo, induction of hyperuricemia increased the incidence of AAA formation and the abdominal aortic diameter in mice. The hyperuricemic mice exhibited higher levels of urate transporter 1 (URAT1) expression, phospho-extracellular signal-regulated kinase (p-ERK)1/2 expression, reactive oxygen species (ROS) levels and matrix metalloproteinase (MMP)-9 expression in the abdominal aorta than the control mice. Soluble uric acid increased the expression of URAT1, p-ERK1/2, and MMP-9 and the levels of ROS in HASMCs in vitro.CONCLUSIONS:
We have provided human evidence that hyperuricemia exacerbates AAA formation. In addition, our murine experimental evidence suggests that hyperuricemia exacerbates AAA formation and reveals that the URAT1/ERK1/2/ROS/MMP-9 pathway is among the pathways activated by uric acid in HASMCs.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aneurisma da Aorta Abdominal
/
Hiperuricemia
Tipo de estudo:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
BMC Cardiovasc Disord
Ano de publicação:
2023
Tipo de documento:
Article