Background: The occurrence of thrombotic disease involves many factors, including vascular endothelial injury, hemodynamic changes and changes in blood fluid composition. Abnormal activation of platelets is the core of thrombotic disease [1]. Clinical studies have shown that obesity increases an individual’s risk to suffer potentially lethal atherothrombotic complications such as myocardial infarction or stroke [2] In this regard, Adiponectin, an adipocytokine that is abundantly present in plasma [3,4] but is down-regulated in association with obesity-linked diseases including coronary artery diseases [5,6] Adiponectin function is mediated through its receptors: AdipoR1 and AdipoR2, Whether adiponectin can affect arterial thrombosis by affecting platelet activation remains unknown. AdipoRon is an orally active synthetic molecule which can bind to AdipoR1, AdipoR2 [7].

Aims: By studying the effect of AdipoRon on human platelets, we investigate the mechanism of adiponectin regulation of thrombotic diseases.

Methods: We explore the role of AdipoRon in platelet activation through platelet aggregation, adhesion experiment and flow cytometric analysis; Western blots were used to explore signaling pathway of AdipoRon; Ferric chloride-induced carotid injury model was used to establish the influence of AdipoRon on thrombus formation in vivo.

Results: AdipoRon inhibited the platelet agonist (U46619, Thrombin, Collagen) induced platelet aggregation. In addition, AdipoRon incubation markedly decreased the surface area of spread platelets (Fig.1). Western blot assays revealed that AdipoRon regulated platelet activation via AMPK, PI3K/Akt and ERK1/2 pathway (Fig.2A). The occlusion time in mice that received AdipoRon was 586.8± 43.73s which was remarkably different from that of the vehicle-treated group 242.5± 23.09s(Fig. 2B).

Conclusions: AdipoRon inhibited platelet activation mainly through the adiponectin receptors AdipoR1, ultimately inhibiting platelet activation via PI3K/Akt and ERK1/2 pathway, AdipoRon also inhibit arterial thrombosis in vivo. Further study of the signaling pathway of AdipRon is conducive to the development of anti-platelet drugs.

[Figure1]

[Fig.2A and fig.2B]

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/the-inhibitory-mechanism-of-adiporon-during-platelet-activation/