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

Autor: Carnevale R; Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy., Bartimoccia S; Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy., Nocella C; Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy., Di Santo S; Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy., Loffredo L; Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy., Illuminati G; The 'Francesco Durante' Department of Surgery, 'La Sapienza' University, Rome, Italy., Lombardi E; Vascular Biology and Stem Cells Unit, Centro di Riferimento Oncologico, Aviano, Italy., Boz V; Vascular Biology and Stem Cells Unit, Centro di Riferimento Oncologico, Aviano, Italy., Del Ben M; Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy., De Marco L; Vascular Biology and Stem Cells Unit, Centro di Riferimento Oncologico, Aviano, Italy., Pignatelli P; Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy., Violi F; Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy. Electronic address: francesco.violi@uniroma1.it.
Jazyk: angličtina
Zdroj: Atherosclerosis [Atherosclerosis] 2014 Nov; Vol. 237 (1), pp. 108-16. Date of Electronic Publication: 2014 Sep 09.
DOI: 10.1016/j.atherosclerosis.2014.08.041
Abstrakt: 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 (57.14 μmol/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-ΙΙΙ 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, p47(phox) 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.
(Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: