Store-operated calcium entry in thrombosis and thrombo-inflammation

Cell Calcium. 2019 Jan;77:39-48. doi: 10.1016/j.ceca.2018.11.005. Epub 2018 Nov 23.

Abstract

Cytosolic free calcium (Ca2+) is a second messenger regulating a wide variety of functions in blood cells, including adhesion, activation, proliferation and migration. Store-operated Ca2+ entry (SOCE), triggered by depletion of Ca2+ from the endoplasmic reticulum, provides a main mechanism of regulated Ca2+ influx in blood cells. SOCE is mediated and regulated by isoforms of the ion channel proteins ORAI and TRP, and the transmembrane Ca2+ sensors stromal interaction molecules (STIMs), respectively. This report provides an overview of the (patho)physiological importance of SOCE in blood cells implicated in thrombosis and thrombo-inflammation, i.e. platelets and immune cells. We also discuss the physiological consequences of dysregulated SOCE in platelets and immune cells and the potential of SOCE inhibition as a therapeutic option to prevent or treat arterial thrombosis as well as thrombo-inflammatory disease states such as ischemic stroke.

Keywords: Arterial thrombosis; Immune cells; Ischemic stroke; Platelets; SOCE; Thrombo-inflammation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood Platelets / metabolism*
  • Blood Platelets / pathology
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Calcium / metabolism*
  • Calcium Release Activated Calcium Channels / metabolism*
  • Calcium Signaling*
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum / pathology
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology
  • Stroke / metabolism
  • Stroke / pathology
  • Thrombosis / metabolism*
  • Thrombosis / pathology

Substances

  • Calcium Release Activated Calcium Channels
  • Calcium