Plasma L5 levels are elevated in ischemic stroke patients and enhance platelet aggregation

Ming Yi Shen, Fang Yu Chen, Jing Fang Hsu, Ru Huei Fu, Chia Ming Chang, Chiz Tzung Chang, Chung Hsiang Liu, Jia Rong Wu, An Sheng Lee, Hua Chen Chan, Joen Rong Sheu, Shinn Zong Lin, Woei Cherng Shyu, Tatsuya Sawamura, Kuan Cheng Chang, Chung Y. Hsu, Chu Huang Chen

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31 Citations (Scopus)

Abstract

L5, the most electronegative and atherogenic subfraction of low-density lipoprotein (LDL), induces platelet activation. We hypothesized that plasma L5 levels are increased in acute ischemic stroke patients and examined whether lectin-like oxidized LDL receptor-1 (LOX-1), the receptor for L5 on endothelial cells and platelets, plays a critical role in stroke. Because amyloid b (Ab) stimulates platelet aggregation, we studied whether L5 and Ab function synergistically to induce prothrombotic pathways leading to stroke. Levels of plasma L5, serum Ab, and platelet LOX-1 expression were significantly higher in acute ischemic stroke patients than in controls without metabolic syndrome (P <.01). In mice subjected to focal cerebral ischemia, L5 treatment resulted in larger infarction volumes than did phosphatebuffered saline treatment. Deficiency or neutralizing of LOX-1 reduced infarct volume up to threefoldafter focal cerebral ischemiainmice, illustrating the importanceofLOX-1in stroke injury. In human platelets, L5 but not L1 (the least electronegative LDL subfraction) induced Ab release via IkBkinase 2 (IKK2). Furthermore, L51Ab synergistically induced glycoprotein IIb/IIIa receptor activation; phosphorylation of IKK2, IkBa, p65, and c-Jun N-Terminal kinase 1; and platelet aggregation. These effectswere blockedby inhibiting IKK2,LOX-1,ornuclear factor'kB(NF-kB). InjectingL51Abshortenedtail-bleeding timeby50%(n512;P

Original languageEnglish
Pages (from-to)1336-1345
Number of pages10
JournalBlood
Volume127
Issue number10
DOIs
Publication statusPublished - Mar 10 2016
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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    Shen, M. Y., Chen, F. Y., Hsu, J. F., Fu, R. H., Chang, C. M., Chang, C. T., Liu, C. H., Wu, J. R., Lee, A. S., Chan, H. C., Sheu, J. R., Lin, S. Z., Shyu, W. C., Sawamura, T., Chang, K. C., Hsu, C. Y., & Chen, C. H. (2016). Plasma L5 levels are elevated in ischemic stroke patients and enhance platelet aggregation. Blood, 127(10), 1336-1345. https://doi.org/10.1182/blood-2015-05-646117