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Kazuyo Yamaji, Krishna Pada Sarker, Koichi Kawahara, Satoshi Iino, Munekazu Yamakuchi, Kazuhiro Abeyama, Teruto Hashiguchi, Ikuro Maruyama
Anandamide induces apoptosis in human endothelial cells: its regulation system and clinical implications
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 I- converting enzyme (ICE)CED-3 family protease (caspase-3) activity. AEA-induced EC death was inhibited by a selective vanilloid receptor 1 (VR1) antagonist, capsazepine, and was enhanced by a VR1 agonist, capsaicin, indicating that AEA induces apoptosis in ECs via VR1. 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.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 89, 05/2003
Pages: 875 - 884