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Advanced glycation end products induce senescence of atrial myocytes and increase susceptibility of atrial fibrillation in diabetic mice.
Zheng, Dan-Lin; Wu, Qing-Rui; Zeng, Peng; Li, Sui-Min; Cai, Yong-Jiang; Chen, Shu-Zhen; Luo, Xue-Shan; Kuang, Su-Juan; Rao, Fang; Lai, Ying-Yu; Zhou, Meng-Yuan; Wu, Fei-Long; Yang, Hui; Deng, Chun-Yu.
Afiliación
  • Zheng DL; Guangdong Provincial Key Laboratory of Clinical Pharmacology, Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • Wu QR; Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • Zeng P; Guangdong Provincial Key Laboratory of Clinical Pharmacology, Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • Li SM; Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • Cai YJ; School of Medicine, South China University of Technology, Guangzhou, China.
  • Chen SZ; Guangdong Provincial Key Laboratory of Clinical Pharmacology, Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • Luo XS; Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • Kuang SJ; School of Medicine, South China University of Technology, Guangzhou, China.
  • Rao F; Guangdong Provincial Key Laboratory of Clinical Pharmacology, Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • Lai YY; Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • Zhou MY; Guangdong Provincial Key Laboratory of Clinical Pharmacology, Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • Wu FL; Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • Yang H; School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
  • Deng CY; Guangdong Provincial Key Laboratory of Clinical Pharmacology, Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Aging Cell ; 21(12): e13734, 2022 Dec.
Article en En | MEDLINE | ID: mdl-36278684
Diabetes mellitus (DM) is a common chronic metabolic disease caused by significant accumulation of advanced glycation end products (AGEs). Atrial fibrillation (AF) is a common cardiovascular complication of DM. Here, we aim to clarify the role and mechanism of atrial myocyte senescence in the susceptibility of AF in diabetes. Rapid transesophageal atrial pacing was used to monitor the susceptibility of mice to AF. Whole-cell patch-clamp was employed to record the action potential (AP) and ion channels in single HL-1 cell and mouse atrial myocytes. More importantly, anti-RAGE antibody and RAGE-siRNA AAV9 were used to investigate the relationship among diabetes, aging, and AF. The results showed that elevated levels of p16 and retinoblastoma (Rb) protein in the atrium were associated with increased susceptibility to AF in diabetic mice. Mechanistically, AGEs increased p16/Rb protein expression and the number of SA-ß-gal-positive cells, prolonged the action potential duration (APD), reduced protein levels of Cav1.2, Kv1.5, and current density of ICa,L , IKur in HL-1 cells. Anti-RAGE antibody or RAGE-siRNA AAV9 reversed these effects in vitro and in vivo, respectively. Furthermore, downregulating p16 or Rb by siRNA prevented AGEs-mediated reduction of Cav1.2 and Kv1.5 proteins expression. In conclusion, AGEs accelerated atrial electrical remodeling and cellular senescence, contributing to increased AF susceptibility by activating the p16/Rb pathway. Inhibition of RAGE or the p16/Rb pathway may be a potential therapeutic target for AF in diabetes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fibrilación Atrial / Diabetes Mellitus Experimental / Remodelación Atrial 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
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fibrilación Atrial / Diabetes Mellitus Experimental / Remodelación Atrial Límite: Animals Idioma: En Revista: Aging Cell Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido