Polydatin mitigates thrombosis by inhibiting PHD2-induced proline hydroxylation on collagen, reducing platelet adhesion.
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Key Findings
Abstract
BACKGROUND: Platelet adhesion to collagen, a critical initial step in thrombus formation, remains an underexplored therapeutic target in thrombosis. Current disease treatment strategies primarily focus on platelet activation and aggregation, often overlooking the crucial initial adhesion phase. Reynoutria japonica (Huzhang, HZ), utilized in traditional Chinese medicine to enhance blood circulation and resolve blood stasis, lacks comprehensive insights into its active components and their anti-thrombotic mechanisms. PURPOSE: This study investigated the antithrombotic effects and mechanisms of polydatin, a stilbene derived from HZ, with a focus on its effect on platelet adhesion. METHODS: An acute pulmonary infection model was used, along with metabolomic and proteomic analyses, to investigate the antithrombotic efficacy of the active component polydatin and identify its targets. Chemical biology, protein mass spectrometry analyses, and molecular interaction analysis were performed to investigate its mechanism. Multiple models of circulatory disorders, including disseminated intravascular coagulation (DIC) and atherosclerosis in mice, with or without targeted gene knockdown, were employed to assess the role of polydatin in modulating platelet adhesion. RESULTS: Our investigation revealed that polydatin targets prolyl hydroxylase 2 (PHD2), thereby inhibiting hydroxylation of proline residues on collagen. This disruption in collagen assembly and the von Willebrand factor (VWF)-collagen interaction reduces platelet adhesion, significantly impacting circulation in both DIC and atherosclerosis. This represents a novel mechanism of antithrombotic action, distinct from currently available therapies. CONCLUSION: Targeting PHD2 to modulate collagen structure and platelet adhesion presents a promising novel therapeutic strategy for thrombosis-related circulatory disorders.
Affiliation
Kaixin Liu
External References
- PubMed ID:
- 39826283
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