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Thromb Haemost 2003; 89(05): 875-884
DOI: 10.1055/s-0037-1613475
Wound Healing and Inflammation/Infection
Schattauer GmbH

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

Kazuyo Yamaji
1   Department of Laboratory and Molecular Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
,
Krishna Pada Sarker
1   Department of Laboratory and Molecular Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
,
Koichi Kawahara
1   Department of Laboratory and Molecular Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
,
Satoshi Iino
1   Department of Laboratory and Molecular Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
,
Munekazu Yamakuchi
1   Department of Laboratory and Molecular Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
,
Kazuhiro Abeyama
1   Department of Laboratory and Molecular Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
,
Teruto Hashiguchi
1   Department of Laboratory and Molecular Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
,
Ikuro Maruyama
1   Department of Laboratory and Molecular Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
› Author Affiliations
Further Information

Publication History

Received 24 September 2002

Accepted after revision 27 February 2003

Publication Date:
09 December 2017 (online)

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Summary

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 1β–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.

Keywords

Anandamide - endothelial cell - apoptosis - vanilloid receptor 1 - endotoxin shock
 

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