Vitamin D deficiency enhances platelet activation and thrombosis by regulating VDR/Akt pathway based on platelet proteomics.

European journal of pharmacology [Eur J Pharmacol] 2025 Jul 15; Vol. 999, pp. 177684. Date of Electronic Publication: 2025 May 01.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Scope: Vitamin D deficiency (VDD) is a worldwide pandemic. Pleiotropic effects of vitamin D beyond calcium homeostasis have been shown. However, the direct impact of VDD on platelet reactivity and thrombus formation, as well as the underlying mechanisms, remain vague.
Methods and Results: 427 acute coronary syndrome patients undergoing percutaneous coronary intervention were enrolled in the study. The platelet proteome was analyzed using a four-dimensional data-independent assessment. Platelet function and FeCl 3 -induced carotid artery thrombosis were investigated in the VDD rats. Lower vitamin D quartiles (<16.45 ng/mL) were independently associated with high on-treatment platelet reactivity (adjusted OR 4.21 [95 %CI 1.74-10.15, P = 0.001]). Differential proteins were related to platelet activation, PI3K-Akt pathway, and Vitamin D receptor (VDR). Platelet function was enhanced in diet-induced VDD rats. VDD accelerated FeCl 3 -induced carotid artery thrombosis and shortened tail bleeding time. Mechanism studies revealed that VDD may exert its destructive effect by inactivating the VDR and augmenting p-Akt expression.
Conclusion: VDD was independently related to high on-treatment platelet reactivity among acute coronary syndrome patients undergoing percutaneous coronary intervention. VDD enhanced platelet function and thrombosis by activating the VDR/Akt signaling pathway. Vitamin D replacement therapy could partly reverse these changes, making it a theoretical basis for the prevention of VDD-related thrombotic disease.
(Copyright © 2025 Elsevier B.V. All rights reserved.)

English

Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 1254354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0712 (Electronic) Linking ISSN: 00142999 NLM ISO Abbreviation: Eur J Pharmacol Subsets: MEDLINE

Proto-Oncogene Proteins c-akt*/metabolism , Platelet Activation* , Vitamin D Deficiency*/blood , Vitamin D Deficiency*/complications , Receptors, Calcitriol*/metabolism , Proteomics* , Blood Platelets*/metabolism , Blood Platelets*/drug effects , Thrombosis*/blood , Thrombosis*/etiology , Thrombosis*/metabolism, Animals ; Male ; Humans ; Rats ; Middle Aged ; Signal Transduction ; Female ; Acute Coronary Syndrome/blood ; Aged ; Rats, Sprague-Dawley ; Vitamin D/blood ; Percutaneous Coronary Intervention

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