2. Academic Validation
  3. Adiponectin receptor agonist AdipoRon modulates human and mouse platelet function

Adiponectin receptor agonist AdipoRon modulates human and mouse platelet function

  • Acta Pharmacol Sin. 2022 Aug 2. doi: 10.1038/s41401-022-00943-1.
Xiang-Hui Zhou  # 1 2,  Zhi-Peng Cheng  # 1 2,  Meng Lu 3,  Wen-Yi Lin 1 2,  Li-Li Luo 1 2,  Zhang-Yin Ming 3 4,  Yu Hu 5 6 7
Affiliations

Affiliations

  • 1 Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 2 Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 3 Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 4 Tongji-Rongcheng Center for Biomedicine, Huazhong University of Science and Technology, Wuhan, 430030, China.
  • 5 Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. huyu_whuh@hust.edu.cn.
  • 6 Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, 430030, China. huyu_whuh@hust.edu.cn.
  • 7 Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease, Wuhan, 430022, China. huyu_whuh@hust.edu.cn.
  • # Contributed equally.
PMID: 35918410 DOI: 10.1038/s41401-022-00943-1
Abstract

Adiponectin, an adipokine secreted by adipocytes, has anti-atherosclerotic and antithrombotic activities. AdipoRon is synthetic small molecule Adiponectin Receptor Agonist. In this study, we investigated the effect of AdipoRon on platelet activation and thrombus formation. Washed human platelets were prepared from the peripheral blood of healthy donors. In a series of in vitro platelet functional assays, pre-treatment with AdipoRon (10, 20, 40 µg/mL) dose-dependently inhibited the aggregation, granule secretion and spreading of washed human platelets. We showed that AdipoRon (20, 40 µg/mL) significantly inhibited AMPK, Syk, PLCγ2, PI3K, Akt, p38-MAPK and ERK1/2 signalling pathways in washed human platelets. In addition, we demonstrated that the phosphorylation of CKII at Tyr255 was an important mechanism of the Integrin αIIbβ3-mediated platelet activation. Meanwhile, AdipoR1 deficiency impaired the inhibitory effect of AdipoRon on mouse platelets. In ferric chloride-induced carotid injury model, injection of AdipoRon (5 or 12.5 mg/kg, iv) significantly attenuated arterial thrombosis. In conclusion, AdipoRon attenuates platelet function via the AdipoR1/AMPK/CKII/PI3K/Akt signalling pathways, while exerting a protective effect against arterial thrombosis. This study offers new insights into the fields of Cardiovascular Disease and antiplatelet drug discovery.Schematic model of AdipoRon regulating platelet activation. (BioRender.com).

Keywords

adipoRon; adiponectin; antiplatelet drug; platelet activation; signalling pathway; thrombosis.

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