Cocaine and specific cocaine metabolites induce von Willebrand factor release from endothelial cells in a tissue-specific manner.
Cocaine and specific cocaine metabolites induce von Willebrand factor release from endothelial cells in a tissue-specific manner.
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DOI：
10.1161/atvbaha.113.301436
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发表时间：
2013-06
期刊：
影响因子：
--
通讯作者：
López JA
中科院分区：
文献类型：
--
作者：
Hobbs WE;Moore EE;Penkala RA;Bolgiano DD;López JA
Cocaine use is associated with arterial thrombosis, including myocardial infarction and stroke. Cocaine use results in increased plasma von Willebrand Factor (VWF), accelerated atherosclerosis, and platelet-rich arterial thrombi, suggesting that cocaine activates the endothelium, promoting platelet-VWF interactions. Human umbilical vein (HUVEC), brain microvasculature (BMVEC), or coronary artery (CAEC) endothelial cells were treated with cocaine or metabolites benzoylecgonine, cocaethylene, norcocaine, or ecgonine methylester. Supernatant VWF concentration and multimer structure were measured, and platelet–VWF strings formed on the endothelial surface under flow were quantified. Cocaine, benzoylecgonine, and cocaethylene induced endothelial VWF release, with the two metabolites being more potent than the parent molecule. BMVEC were more sensitive to cocaine and metabolites than were HUVEC or CAEC. CAEC released VWF into the supernatant but did not form VWF–platelet strings. Intracellular cAMP concentration was not increased after treatment with cocaine or its metabolites. Both cocaine and metabolites benzoylecgonine and cocaethylene induced endothelial VWF secretion, possibly explaining thrombotic risk after cocaine ingestion. VWF secretion is likely to vary between vascular beds, with brain endothelial cells being particularly sensitive. These results suggest that clinical management of cocaine-induced ischemia may benefit from therapies aimed at disrupting the VWF–platelet interaction.
