LDL oxidation by platelets propagates platelet activation via an oxidative stress-mediated mechanism

Roberto Carnevale, Simona Bartimoccia, Cristina Nocella, Serena Di Santo, Lorenzo Loffredo, Giulio Illuminati, Elisabetta Lombardi, Valentina Boz, Maria Del Ben, Luigi De Marco, Pasquale Pignatelli, Francesco Violi

Research output: Contribution to journalArticlepeer-review


Objectives: Platelets generate oxidized LDL (ox-LDL) via NOX2-derived oxidative stress. We investigated if once generated by activated platelets ox-LDL can propagate platelet activation. Methods: Experiments were performed in platelets from healthy subjects (HS), hyper-cholesterolemic patients and patients with NOX2 hereditary deficiency. Results: Agonist-stimulated platelets from HS added with LDL were associated with a dose-dependent increase of reactive oxidant species and ox-LDL. Agonist-stimulated platelets from HS added with a fixed dose of LDL (57.14μmol/L) or added with homogenized human atherosclerotic plaque showed enhanced ox-LDL formation (approximately+50% and+30% respectively), which was lowered by a NOX2 inhibitor (approximately-35% and-25% respectively). Compared to HS, ox-LDL production was more pronounced in agonist-stimulated platelet rich plasma (PRP) from hyper-cholesterolemic patients but was almost absent in PRP from NOX2-deficient patients. Platelet aggregation and 8-iso-PGF2α-III formation increased in LDL-treated washed platelets (+42% and+53% respectively) and PRP (+31% and+53% respectively). Also, LDL enhanced platelet-dependent thrombosis at arterial shear rate (+33%) but did not affect platelet activation in NOX2-deficient patients. Platelet activation by LDL was significantly inhibited by CD36 or LOX1 blocking peptides, two ox-LDL receptor antagonists, or by a NOX2 inhibitor. LDL-added platelets showed increased p38MAPK (+59%) and PKC (+51%) phosphorylation, p47phox translocation to platelet membrane (+34%) and NOX2 activation (+30%), which were inhibited by ox-LDL receptor antagonists. Conclusion: Platelets oxidize LDL, which in turn amplify platelet activation via specific ox-LDL receptors; both effects are mediated by NOX2 activation.

Original languageEnglish
Pages (from-to)108-116
Number of pages9
Issue number1
Publication statusPublished - Nov 1 2014


  • Atherosclerosis
  • NADPH oxidase
  • Ox-LDL
  • Oxidative stress

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)


Dive into the research topics of 'LDL oxidation by platelets propagates platelet activation via an oxidative stress-mediated mechanism'. Together they form a unique fingerprint.

Cite this