Your browser doesn't support javascript.
loading
Fibronectin type III domain-containing 5 improves aging-related cardiac dysfunction in mice.
Hu, Can; Zhang, Xin; Hu, Min; Teng, Teng; Yuan, Yu-Pei; Song, Peng; Kong, Chun-Yan; Xu, Si-Chi; Ma, Zhen-Guo; Tang, Qi-Zhu.
Afiliación
  • Hu C; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
  • Zhang X; Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, China.
  • Hu M; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
  • Teng T; Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, China.
  • Yuan YP; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
  • Song P; Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, China.
  • Kong CY; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
  • Xu SC; Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, China.
  • Ma ZG; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
  • Tang QZ; Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, China.
Aging Cell ; 21(3): e13556, 2022 03.
Article en En | MEDLINE | ID: mdl-35166002
Aging is an important risk factor for cardiovascular diseases, and aging-related cardiac dysfunction serves as a major determinant of morbidity and mortality in elderly populations. Our previous study has identified fibronectin type III domain-containing 5 (FNDC5) and its cleaved form, irisin, as the cardioprotectant against doxorubicin-induced cardiomyopathy. Herein, aging or matched young mice were overexpressed with FNDC5 by adeno-associated virus serotype 9 (AAV9) vectors, or subcutaneously infused with irisin to uncover the role of FNDC5 in aging-related cardiac dysfunction. To verify the involvement of nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) and AMP-activated protein kinase α (AMPKα), Nlrp3 or Ampkα2 global knockout mice were used. Besides, young mice were injected with AAV9-FNDC5 and maintained for 12 months to determine the preventive effect of FNDC5. Moreover, neonatal rat cardiomyocytes were stimulated with tumor necrosis factor-α (TNF-α) to examine the role of FNDC5 in vitro. We found that FNDC5 was downregulated in aging hearts. Cardiac-specific overexpression of FNDC5 or irisin infusion significantly suppressed NLRP3 inflammasome and cardiac inflammation, thereby attenuating aging-related cardiac remodeling and dysfunction. In addition, irisin treatment also inhibited cellular senescence in TNF-α-stimulated cardiomyocytes in vitro. Mechanistically, FNDC5 activated AMPKα through blocking the lysosomal degradation of glucagon-like peptide-1 receptor. More importantly, FNDC5 gene transfer in early life could delay the onset of cardiac dysfunction during aging process. We prove that FNDC5 improves aging-related cardiac dysfunction by activating AMPKα, and it might be a promising therapeutic target to support cardiovascular health in elderly populations.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dominio de Fibronectina del Tipo III / Cardiopatías Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Aging Cell Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dominio de Fibronectina del Tipo III / Cardiopatías Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Aging Cell Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido