title: Oxidized low-density lipoprotein-dependent platelet-derived microvesicles trigger procoagulant effects and amplify oxidative stress.
abstract: The fundamental mechanisms that underlie platelet activation in atherothrombosis are still obscure. Oxidative stress is involved in central features of atherosclerosis. Platelet-derived microvesicles (PMVs) could be important mediators between oxidative stress and platelet activation. CD36 could be a receptor of PMVs, thus generating a PMV-CD36 complex. We aimed to investigate the detailed pathway by which oxidative damage contributes to platelet activation by the PMV-CD36 complex. We found that oxidized low-density lipoprotein stimulated the generation of PMVs. PMVs enhanced normal platelet activation, as assessed by the expression of integrin α(IIb)β₃, secretion of soluble P-selectin and platelet aggregation, but CD36-deficient platelets were not activated by PMVs. The function of the PMV-CD36 complex was mediated by the MKK4/JNK2 signaling axis. Meanwhile, PMVs increased the level of 8-iso-prostaglandin-F2α, a marker of oxidative stress, in a CD36- and phosphatidylserine-dependent manner. We concluded that PMVs are important mediators between oxidative stress and platelet activation. PMVs and CD36 may be effective targets for preventing platelet activation in cardiovascular diseases.
authors: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, China.
authors: Hua
authors: H
authors: Wang
authors: Zhi-Hao
authors: ZH
authors: Wang
authors: Jing
authors: J
authors: Kong
authors: Meng-Yun
authors: MY
authors: Yang
authors: Gui-Hua
authors: GH
authors: Jiang
authors: Xu-Ping
authors: XP
authors: Wang
authors: Ming
authors: M
authors: Zhong
authors: Yun
authors: Y
authors: Zhang
authors: Jing-Ti
authors: JT
authors: Deng
authors: Wei
authors: W
authors: Zhang
mesh_terms: D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018955:CD36 Antigens / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D015539:Platelet Activation / Q000187:drug effects
chemical_list: D018955:CD36 Antigens; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein