Phospholipase D1 and D2 synergistically regulate thrombus formation

Li Ming Lien, Wan Jung Lu, Ting Yu Chen, Tzu Yin Lee, Hsueh Hsiao Wang, Hsien Yu Peng, Ray Jade Chen, Kuan Hung Lin

Research output: Contribution to journalArticlepeer-review

Abstract

Previously, we reported that phospholipase D1 (PLD1) and PLD2 inhibition by selective PLD1 and PLD2 inhibitors could prevent platelet aggregation in humans, but not in mice. Moreover, only the PLD1 inhibitor, but not PLD2 inhibitor, could effectively prevent thrombus formation in mice, indicating that PLD might play different roles in platelet function in humans and mice. Although PLD1 and PLD2 were reported to be implicated in thrombotic events, the role of PLD in mice remains not completely clear. Here, we investigated the role of PLD1 and PLD2 in acute pulmonary thrombosis and transient middle cerebral artery occlusion-induced brain injury in mice. The data revealed that inhibition of PLD1, but not of PLD2, could partially prevent pulmonary thrombosis-induced death. Moreover, concurrent PLD1 and PLD2 inhibition could considerably increase survival rate. Likewise, inhibition of PLD1, but not PLD2, partially improved ischemic stroke and concurrent inhibition of PLD1, and PLD2 exhibited a relatively better protection against ischemic stroke, as evidenced by the infarct size, brain edema, modified neurological severity score, rotarod test, and the open field test. In conclusion, PLD1 might play a more important role than PLD2, and both PLD1 and PLD2 could act synergistically or have partially redundant functions in regulating thrombosis-relevant events.

Original languageEnglish
Article number6954
Pages (from-to)1-13
Number of pages13
JournalInternational journal of molecular sciences
Volume21
Issue number18
DOIs
Publication statusPublished - Sep 2 2020

Keywords

  • Middle cerebral artery occlusion
  • Phospholipase D
  • Platelet
  • Thrombosis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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