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Thrombopoietin Contributes to Enhanced Platelet Activation in Patients with Type 1 Diabetes Mellitus

Ornella Bosco1, Barbara Vizio1, Gabriella Gruden1

  • 1Department of Medical Sciences, University of Turin, 10126 Turin, Italy.

International Journal of Molecular Sciences
|July 2, 2021
PubMed

Insights

Elevated thrombopoietin (THPO) in type 1 diabetes mellitus (T1DM) enhances platelet activation and binding to leukocytes. This may contribute to the increased atherosclerotic cardiovascular disease risk in T1DM patients.

Area of Science:

  • Endocrinology
  • Hematology
  • Cardiovascular Medicine

Background:

  • Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death in type 1 diabetes mellitus (T1DM).
  • Increased platelet reactivity contributes significantly to the heightened atherothrombotic risk observed in diabetic individuals.
  • Thrombopoietin (THPO), a key regulator of platelet production, also influences mature platelet function, including activation and leukocyte binding.

Purpose of the Study:

  • To investigate the role of elevated thrombopoietin (THPO) levels in platelet activation in patients with type 1 diabetes mellitus (T1DM).
  • To assess the correlation between THPO levels and markers of platelet activation and glycemic control in T1DM.
  • To evaluate the in vitro effect of T1DM plasma on platelet-leukocyte interactions and the specific role of THPO in this process.

Main Methods:

  • Compared plasma THPO levels, platelet-leukocyte binding, P-selectin expression, and THPO receptor (THPOR) expression between 28 T1DM patients and 28 healthy controls.
  • Assessed the priming effect of plasma from T1DM patients and controls on platelet-leukocyte binding and P-selectin expression in vitro.
  • Investigated the role of THPO in mediating these effects using a specific THPO inhibitor.

Main Results:

  • T1DM patients exhibited significantly higher plasma THPO levels compared to healthy subjects.
  • Increased platelet-monocyte and platelet-granulocyte binding, along with elevated platelet P-selectin expression, were observed in T1DM patients.
  • THPO concentrations positively correlated with platelet-leukocyte binding and glycemic control markers (fasting glucose, HbA1c).
  • In vitro studies demonstrated that T1DM plasma primed platelet-leukocyte binding and P-selectin expression, an effect abrogated by THPO inhibition.

Conclusions:

  • Augmented circulating THPO levels in T1DM patients may enhance platelet activation and pro-thrombotic potential.
  • These findings suggest that THPO plays a significant role in the increased atherosclerotic risk associated with type 1 diabetes mellitus.
  • Targeting THPO activity could represent a potential therapeutic strategy to mitigate cardiovascular risk in T1DM.

Keywords:
atherosclerotic cardiovascular diseasesplatelet activation markersplatelet–leukocyte adhesionthrombopoietintype 1 diabetes mellitus

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