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Molecular Medicine

, Volume 18, Issue 2, pp 159–166 | Cite as

Oxidized Low-Density Lipoprotein-Dependent Platelet-Derived Microvesicles Trigger Procoagulant Effects and Amplify Oxidative Stress

  • Hua Wang
  • Zhi-Hao Wang
  • Jing Kong
  • Meng-Yun Yang
  • Gui-Hua Jiang
  • Xu-Ping Wang
  • Ming Zhong
  • Yun Zhang
  • Jing-Ti Deng
  • Wei Zhang
Research Article

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 αIIbβ3, 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.

Notes

Acknowledgments

This work was supported by research grants from the Key Technologies Research and Development Program of Shandong Province (2006GG2202020 and 2010G0020262), the Natural Science Foundation of Shandong Province (Y2005C11, ZR2009CM022, ZR2009CM025 and BS2009YY026), the National Natural Science Foundation of China (30670874, 30871038, 30971215, 81070192 and 81070141) and the National Basic Research Program of China (973 Program, Grant no. 2009CB521904).

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Authors and Affiliations

  • Hua Wang
    • 1
  • Zhi-Hao Wang
    • 1
  • Jing Kong
    • 1
  • Meng-Yun Yang
    • 1
  • Gui-Hua Jiang
    • 1
  • Xu-Ping Wang
    • 1
  • Ming Zhong
    • 1
  • Yun Zhang
    • 1
  • Jing-Ti Deng
    • 2
  • Wei Zhang
    • 1
  1. 1.Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of CardiologyQilu Hospital of Shandong UniversityJi’nanChina
  2. 2.Department of Biochemistry and Molecular Biology, Faculty of MedicineUniversity of CalgaryNW CalgaryCanada

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