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Elabela-apelin-12, 17, 36/APJ system promotes platelet aggregation and thrombosis via activating the PANX1-P2X7 signaling pathway.
Chen, Zhe; Luo, Xuling; Liu, Meiqing; Jiang, Jinyong; Li, Yao; Huang, Zhen; Wang, Lingzhi; Cao, Jiangang; He, Lu; Huang, Shifang; Hu, Haoliang; Li, Lanfang; Chen, Linxi.
Afiliación
  • Chen Z; Hunan Provincial Key Laboratory of tumor microenvironment responsive drug research, Hengyang Medical School, Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China.
  • Luo X; Hunan Provincial Key Laboratory of tumor microenvironment responsive drug research, Hengyang Medical School, Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China.
  • Liu M; Hunan Provincial Key Laboratory of tumor microenvironment responsive drug research, Hengyang Medical School, Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China.
  • Jiang J; Hunan Provincial Key Laboratory of tumor microenvironment responsive drug research, Hengyang Medical School, Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China.
  • Li Y; Hunan Provincial Key Laboratory of tumor microenvironment responsive drug research, Hengyang Medical School, Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China.
  • Huang Z; Hunan Provincial Key Laboratory of tumor microenvironment responsive drug research, Hengyang Medical School, Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China.
  • Wang L; Hunan Provincial Key Laboratory of tumor microenvironment responsive drug research, Hengyang Medical School, Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China.
  • Cao J; Hunan Provincial Key Laboratory of tumor microenvironment responsive drug research, Hengyang Medical School, Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China.
  • He L; Hunan Provincial Key Laboratory of tumor microenvironment responsive drug research, Hengyang Medical School, Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China.
  • Huang S; Hunan Provincial Key Laboratory of tumor microenvironment responsive drug research, Hengyang Medical School, Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China.
  • Hu H; Hunan Provincial Key Laboratory of tumor microenvironment responsive drug research, Hengyang Medical School, Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China.
  • Li L; Changde Research Center for Artificial Intelligence and Biomedicine, College of Life and Environmental Sciences, Hunan University of Arts and Science, Changde, Hunan, China.
  • Chen L; Hunan Provincial Key Laboratory of tumor microenvironment responsive drug research, Hengyang Medical School, Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China.
J Cell Biochem ; 124(4): 586-605, 2023 04.
Article en En | MEDLINE | ID: mdl-36855998
ABSTRACT
The elabela-apelin/angiotensin domain type 1 receptor-associated protein (APJ) system is an important regulator in certain thrombosis-related diseases such as atherosclerosis, myocardial infarction, and cerebral infarction. Our previous reports have revealed that apelin exacerbates atherosclerotic lesions. However, the relationship between the elabela-apelin/APJ system and platelet aggregation and atherothrombosis is unclear. The results of the present study demonstrate that elabela and other endogenous ligands such as apelin-12, -17, and -36 induce platelet aggregation and thrombosis by activating the pannexin1(PANX1)-P2X7 signaling pathway. Interestingly, the diuretic, spironolactone, a novel PANX1 inhibitor, alleviated elabela- and apelin isoforms-induced platelet aggregation and thrombosis. Significantly, two potential antithrombotic drugs were screened out by targeting APJ receptors, including the anti-HIV ancillary drug cobicistat and the traditional Chinese medicine monomer Schisandrin A. Both cobicistat and Schisandrin A abolished the effects of elabela and apelin isoforms on platelet aggregation, thrombosis, and cerebral infarction. In addition, cobicistat significantly attenuated thrombosis in a ponatinib-induced zebrafish trunk model. Overall, the elabela-apelin/APJ axis mediated platelet aggregation and thrombosis via the PANX1-P2X7 signaling pathway in vitro and in vivo. Blocking the APJ receptor with cobicistat/Schisandrin A or inhibiting PANX1 with spironolactone may provide novel therapeutic strategies against thrombosis.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Trombosis / Hormonas Peptídicas Límite: Animals Idioma: En Revista: J Cell Biochem Año: 2023 Tipo del documento: Article País de afiliación: China
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Trombosis / Hormonas Peptídicas Límite: Animals Idioma: En Revista: J Cell Biochem Año: 2023 Tipo del documento: Article País de afiliación: China