Functional role of soluble receptor for advanced glycation end products in stroke

Sung Chun Tang, Yu Chi Wang, Yu I. Li, Hsiao Ching Lin, Silvia Manzanero, Yu Hsuan Hsieh, Simon Phipps, Chaur Jong Hu, Hung Yi Chiou, Yi Shuian Huang, Wei Shiung Yang, Mark P. Mattson, Thiruma V. Arumugam, Jiann Shing Jeng

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Objective-Little is known about the involvement of the soluble form of receptor for advanced glycation end products (sRAGE) in acute ischemic stroke (IS). Here, we aim to identify the role of plasma sRAGE and high mobility group box 1 (HMGB1) in imaging-confirmed IS patients, as well as mice subjected to focal ischemic stroke. Methods and Results-IS patients were recruited and plasma samples were collected for the measurement of sRAGE and HMGB1 after stroke. The relation of sRAGE and HMGB1 with acute IS was also investigated in a C57BL/6J mouse model of focal ischemic stroke and primary cortical neurons subjected to oxygen and glucose deprivation. Plasma levels of sRAGE and HMGB1 were both significantly increased within 48 hours after IS, and the sRAGE level was an independent predictor of functional outcome at 3 months poststroke. Immunoprecipitation assays revealed that the binding of plasma HMGB1 to sRAGE increased progressively after IS both in patients and mice. Administration of recombinant sRAGE significantly reduced infiltrating immune cells and improved the outcome of injury in mice, protected cultured neurons against oxygen and glucose deprivation-induced cell death, and ameliorated the detrimental effect of recombinant HMGB1. Conclusion-Early poststroke plasma sRAGE may play a protective role in IS by capturing HMGB1. Hence, recombinant sRAGE is a potential therapeutic agent in acute IS.

Original languageEnglish
Pages (from-to)585-594
Number of pages10
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume33
Issue number3
DOIs
Publication statusPublished - Mar 2013

Keywords

  • animal model
  • HMGB1
  • inflammation
  • ischemic stroke
  • sRAGe

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Tang, S. C., Wang, Y. C., Li, Y. I., Lin, H. C., Manzanero, S., Hsieh, Y. H., Phipps, S., Hu, C. J., Chiou, H. Y., Huang, Y. S., Yang, W. S., Mattson, M. P., Arumugam, T. V., & Jeng, J. S. (2013). Functional role of soluble receptor for advanced glycation end products in stroke. Arteriosclerosis, Thrombosis, and Vascular Biology, 33(3), 585-594. https://doi.org/10.1161/ATVBAHA.112.300523