Anandamide induces apoptosis in human endothelial cells: Its regulation system and clinical implications

Kazuyo Yamaji, Krishna Pada Sarker, Koichi Kawahara, Satoshi Iino, Munekazu Yamakuchi, Kazuhiro Abeyama, Teruto Hashiguchi, Ikuro Maruyama

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Anandamide (AEA), an endogenous cannabinoid, is generated by macrophages during shock conditions, and is thought to be a causative mediator of septic shock. Thus, we hypothesized that AEA plays a crucial role in endothelial cell (EC) injury. Here, we demonstrate that AEA induces apoptosis in a time- and dose-dependent manner in human umbilical vein endothelial cells (HUVECs). AEA triggered phosphorylation of c-Jun NH2-terminal kinase (JNK) and p38 mitogen activated protein kinase. AEA also showed a marked increase of interleukin Iβ-converting enzyme (ICE)CED-3 family protease (caspase-3) activity. AEA-induced EC death was inhibited by a selective vanilloid receptor I (VRI) antagonist, capsazepine, and was enhanced by a VRI agonist, capsaicin, indicating that AEA induces apoptosis in ECs via VRI. In conclusion, we propose that AEA may play a crucial role in EC injury under conditions of shock, and that the use of inhibitors of the AEA regulation system may have a therapeutic effect under these conditions.

Original languageEnglish (US)
Pages (from-to)875-884
Number of pages10
JournalThrombosis and Haemostasis
Issue number5
StatePublished - May 1 2003


  • Anandamide
  • Apoptosis
  • Endothelial cell
  • Endotoxin shock
  • Vanilloid receptor I

ASJC Scopus subject areas

  • Hematology


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