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Platelet activation by low concentrations of intact oxidized LDL particles involves the PAF receptor

Rui Chen1, Xi Chen, Robert G Salomon

  • 1Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA.

Arteriosclerosis, Thrombosis, and Vascular Biology
|December 30, 2008
PubMed
Abstract

Insights

Oxidized LDL (oxLDL) activates platelets via the PAF receptor, a response mediated by various oxidized phospholipids. This finding reveals a broader role for the PAF receptor in platelet activation than previously understood.

Area of Science:

  • Cardiovascular Biology
  • Platelet Physiology
  • Lipid Metabolism

Background:

  • Mitochondrial depolarization is a known factor in platelet activation.
  • Oxidized low-density lipoprotein (oxLDL) contains specific oxidized phospholipids that affect mitochondrial function in nucleated cells.
  • It is hypothesized that oxLDL may enhance platelet activation.

Purpose of the Study:

  • To investigate the role of intact oxLDL particles in platelet activation.
  • To identify the specific mechanisms and receptors involved in oxLDL-mediated platelet activation.
  • To determine the range of oxidized phospholipids recognized by the platelet activation pathway.

Main Methods:

  • Flow cytometry was used to assess platelet responses, including intracellular calcium (Ca2+) levels, platelet aggregation, and the expression of activated glycoprotein IIb/IIIa and P-selectin.
  • Platelets were stimulated with oxLDL alone or in combination with subthreshold amounts of soluble agonists.
  • The role of the platelet-activating factor (PAF) receptor was investigated using PAF receptor agonists.

Main Results:

  • Intact oxLDL particles, in synergy with low agonist concentrations, increased intracellular Ca2+, induced platelet aggregation, and promoted the expression of activated markers.
  • oxLDL alone induced platelet aggregation and increased intracellular Ca2+ at lower concentrations.
  • Specific oxidized phospholipids, including hexadecyl azelaoyl-lysoPAF (HAz-LPAF), were identified as potent platelet agonists, activating platelets and depolarizing mitochondria.
  • The PAF receptor was found to be essential for oxLDL-induced platelet activation, recognizing a wider array of oxidized phospholipids than previously expected.

Conclusions:

  • Intact oxLDL particles activate platelets through the platelet-activating factor (PAF) receptor.
  • The PAF receptor demonstrates a broader recognition profile for oxidized phospholipids present in oxLDL than previously anticipated.

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