Convallatoxin, the primary cardiac glycoside in lily of the valley (Convallaria majalis), induces tissue factor expression in endothelial cells

Abstract

Abstract Background Convallotoxin (CNT), present in lily of the valley (Convallaria majalis), is a toxin that causes food poisoning among humans and companion animals. Although various symptoms of CNT poisoning have been well described, hypercoagulability owing to CNT is only empirically known among some veterinarians, and the underlying mechanism remains to be elucidated. CNT exerts cytotoxic effects on endothelial cells. Objectives This study aimed to determine whether CNT induces the expression of tissue factor (TF), a potent initiator of the extrinsic coagulation cascade, in endothelial cells and leads to a hypercoagulable state. Methods Human umbilical vein endothelial cells (HUVECs) were used for in vitro experiments. HUVECs were treated with or without CNT (50 and 100 nM) for 4 h. Phosphate‐buffered saline was used as a control. Cell viability was determined using the WST‐8 assay. Quantitative real‐time polymerase chain reaction was performed to determine TF mRNA expression. TF protein expression was observed using a laser scanning confocal microscope. Results The viability of HUVECs significantly reduced after CNT treatment compared with that of non‐treated cells (p < 0.05). Moreover, a significant increase in TF mRNA and protein expression was observed after 4 h of CNT treatment. CNT elicited these effects in a dose‐dependent manner. Conclusions TF expression induced by CNT in endothelial cells can contribute to the development of a hypercoagulable state. The present study partially revealed the mechanisms underlying the CNT‐induced hypercoagulable state. The findings can contribute to the development of a novel therapy for lily of the valley poisoning.

Keywords

• convallatoxin
• endothelial cells
• hypercoagulability
• lily of the valley
• tissue factor