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Involvement of plasminogen activator inhibitor-1 in p300/p53-mediated age-related atrial fibrosis.
Lai, Yingyu; He, Jintao; Gao, Xiaoyan; Peng, Dewei; Zhou, Huishan; Xu, Yuwen; Luo, Xueshan; Yang, Hui; Zhang, Mengzhen; Deng, Chunyu; Wu, Shulin; Xue, Yumei; Zhou, Feng; Rao, Fang.
Afiliación
  • Lai Y; Medical Research Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
  • He J; Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
  • Gao X; Department of Pharmacy, The People's Hospital of Hezhou, Hezhou, Guangxi, China.
  • Peng D; School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.
  • Zhou H; Medical Research Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
  • Xu Y; Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
  • Luo X; Medical Research Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
  • Yang H; Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
  • Zhang M; Medical Research Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
  • Deng C; Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
  • Wu S; Medical Research Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
  • Xue Y; Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
  • Zhou F; Medical Research Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
  • Rao F; Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
PeerJ ; 11: e16545, 2023.
Article en En | MEDLINE | ID: mdl-38107584
ABSTRACT
Plasminogen activator inhibitor-1 (PAI-1), a key regulator of the fibrinolytic system, is also intimately involved in the fibrosis. Although PAI-1 may be involved in the occurrence of atrial fibrillation (AF) and thrombosis in the elderly, but whether it participated in aging-related atrial fibrosis and the detailed mechanism is still unclear. We compared the transcriptomics data of young (passage 4) versus senescent (passage 14) human atrial fibroblasts and found that PAI-1 was closely related to aging-related fibrosis. Aged mice and senescent human and mouse atrial fibroblasts underwent electrophysiological and biochemical studies. We found that p300, p53, and PAI-1 protein expressions were increased in the atrial tissue of aged mice and senescent human and mouse atrial fibroblasts. Curcumin or C646 (p300 inhibitor), or p300 knockdown inhibited the expression of PAI-1 contributing to reduced atrial fibroblasts senescence, atrial fibrosis, and the AF inducibility. Furthermore, p53 knockdown decreased the protein expression of PAI-1 and p21 in senescent human and mouse atrial fibroblasts. Our results suggest that p300/p53/PAI-1 signaling pathway participates in the mechanism of atrial fibrosis induced by aging, which provides new sights into the treatment of elderly AF.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína p53 Supresora de Tumor / Inhibidor 1 de Activador Plasminogénico Límite: Animals / Humans Idioma: En Revista: PeerJ Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína p53 Supresora de Tumor / Inhibidor 1 de Activador Plasminogénico Límite: Animals / Humans Idioma: En Revista: PeerJ Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos