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Exploring the role of iNOS in HFpEF-Related myocardial fibrosis: Involvement of PTEN-PI3K/AKT signaling pathway.
You, Hongjun; Gou, Qiling; Dong, Mengya; Chang, Fengjun; Xiu, Jiancheng.
Afiliación
  • You H; Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China; Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, China.
  • Gou Q; Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, China.
  • Dong M; Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, China.
  • Chang F; Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, Xi'an, 710068, Shaanxi, China.
  • Xiu J; Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. Electronic address: xiujch@163.com.
Biochem Biophys Res Commun ; 734: 150589, 2024 Aug 22.
Article en En | MEDLINE | ID: mdl-39245028
ABSTRACT

BACKGROUND:

Heart failure with preserved ejection fraction (HFpEF) is a challenging condition to treat with myocardial fibrosis being a pivotal pathological component. Previous studies have suggested a role for inducible nitric oxide synthase (iNOS) in the progression of this condition, but the precise mechanisms remain unclear. This study aimed to investigate the role of iNOS in HFpEF-related myocardial fibrosis and identify potential therapeutic targets.

METHODS:

A 'two-hit' mouse model of HFpEF was established, and echocardiography, histopathology and biochemical analyses were performed. In vitro experiments were conducted in mouse cardiac fibroblasts, with iNOS overexpression and application of iNOS or phosphatidylinositol 3 kinase (PI3K) inhibitors. The iNOS-S-nitrosylated phosphatase and TENsin homolog (SNO-PTEN)-phosphorylated-protein kinase B (p-AKT) pathway was investigated, along with the effects on fibrotic markers and cell proliferation and migration.

RESULTS:

HFpEF mice exhibited significant cardiac dysfunction and fibrosis, with increased expression of iNOS, SNO-PTEN, and p-AKT, indicative of the activation of the iNOS-SNO-PTEN-p-AKT pathway. iNOS overexpression in mouse cardiac fibroblasts led to increased SNO-PTEN, decreased PTEN, activated phosphorylated PI3K (p-PI3K) and p-AKT, and enhanced cell proliferation and migration, as well as increased collagen I and III expression. The use of an iNOS inhibitor (L-NIL) or a PI3K inhibitor (LY294002) partially reversed these changes.

CONCLUSION:

Our findings suggest that the iNOS-SNO-PTEN-p-AKT pathway may play a crucial role in HFpEF-related myocardial fibrosis, with iNOS and PI3K inhibitors offering potential therapeutic benefits. These insights may pave the way for the development of effective drug therapies for HFpEF.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Biochem Biophys Res Commun Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos