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

Thromb Haemost. 2020 May;120(5):768-775. doi: 10.1055/s-0040-1709523. Epub 2020 May 5.

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.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • Blood Platelets / metabolism*
  • Cell Degranulation
  • Female
  • Fibrinogen / metabolism
  • Healthy Volunteers
  • Humans
  • Male
  • P-Selectin / blood
  • Platelet Activation*
  • Platelet Aggregation
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism*
  • Polymorphism, Single Nucleotide
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Signal Transduction
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D Deficiency / blood*
  • Vitamin D Deficiency / diagnosis
  • Vitamin D Deficiency / genetics
  • Young Adult

Substances

  • Biomarkers
  • P-Selectin
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Receptors, Calcitriol
  • SELP protein, human
  • VDR protein, human
  • Vitamin D
  • Fibrinogen
  • 25-hydroxyvitamin D