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Thromb Haemost 2020; 120(05): 768-775
DOI: 10.1055/s-0040-1709523
Cellular Haemostasis and Platelets
Georg Thieme Verlag KG Stuttgart · New York

Platelet Integrin αIIbβ3 Activation is Associated with 25-Hydroxyvitamin D Concentrations in Healthy Adults

Floor E. Aleva
1   Department of Respiratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
2   Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
3   Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands
,
Rahajeng N. Tunjungputri
2   Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
3   Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands
,
Lisa N. van der Vorm
1   Department of Respiratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
4   Synapse Research Institute, Maastricht, The Netherlands
5   Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands
6   Department of Clinical Chemistry and Haematology, GelreZiekenhuizen, Apeldoorn, The Netherlands
,
Yang Li
7   Department of Genetics, University Medical Centre Groningen, Nijmegen, The Netherlands
,
Yvonne F. Heijdra
1   Department of Respiratory Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
,
Marije Oosting
2   Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
3   Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands
,
Sanne P. Smeekens
2   Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
3   Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands
,
Martin Jaeger
2   Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
3   Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands
,
Leo A.B. Joosten
2   Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
3   Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands
,
Philip G. de Groot
2   Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
3   Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands
,
Mihai G. Netea
2   Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
3   Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands
8   Department for Genomics and Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany
,
Andre J.A.M. van der Ven
2   Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
3   Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands
,
Quirijn de Mast
2   Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
3   Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands
› Author Affiliations Funding F.E.A. was supported by a grant from the Lung Foundation Netherlands (Project #5.1.13.033). M.G.N. was supported by an ERC Consolidator Grant (#310372) and a Spinoza Grant of the Netherlands Organization for Scientific Research. Y.L. and M.O. were supported by a VENI grant (# 863.13.011 and 016.176.006) from the Netherlands Organization for Scientific Research (NWO).
Further Information

Publication History

09 November 2019

24 February 2020

Publication Date:
05 May 2020 (online)

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Abstract

Background Cardiovascular events are associated with low circulating vitamin D concentrations, although the underlying mechanisms are poorly understood. This study investigated associations between 25-hydroxyvitamin D concentrations, platelet function, and single-nucleotide polymorphisms (SNPs) in genes influencing vitamin D biology in the 500 Functional Genomics (500FG) cohort.

Methods In this observational study, platelet activation and function were measured by flow cytometry by binding of fibrinogen to the activated fibrinogen receptor integrin αIIbβ3 and expression of P-selectin, markers of platelet aggregation and degranulation, respectively. These parameters were correlated to serum 25-hydroxyvitamin D and genotyping was performed to investigate SNPs in genes important for vitamin D biology.

Results Circulating 25-hydroxyvitamin D concentrations correlated inversely with baseline platelet binding of fibrinogen to integrin αIIbβ3 (Pearson's r= –0.172, p = 0.002) and platelet responses to platelet agonist cross-linked collagen-related peptide (CRP-XL) (Pearson's r= –0.196,p = 0.002). This effect was due to circulating vitamin D levels ≤50nmol/L, since no differences in platelet fibrinogen binding were observed between subjects with normal 25-hydroxyvitamin D concentrations (>75nmol/L) and a 25-hydroxyvitamin D insufficiency (50–75 nmol/L). No correlations between 25-hydroxyvitamin D concentrations and platelet P-selectin expression were found. Several SNPs in the GC region of the vitamin D binding proteingene were associated with platelet responses to CRP-XL.

Conclusion Low circulating vitamin D concentrations are associated with increased platelet fibrinogen binding to integrin αIIbβ3 in unstimulated samples and after stimulation with CRP-XL. These findings may contribute to the increased incidence of cardiovascular events in vitamin D deficient adults and its seasonal variation. Further studies are needed to investigate causality.

Keywords

platelets - vitamin D - inflammation - hemostasis - fibrinogen

Supplementary Material

 

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