|کد مقاله||کد نشریه||سال انتشار||مقاله انگلیسی||ترجمه فارسی||نسخه تمام متن|
|5561683||1562282||2017||9 صفحه PDF||سفارش دهید||دانلود رایگان|
- Varenicline lowers VE-cadherin expression in human endothelial cells (HUVECs).
- Varenicline stimulates migration and MAPK signaling through Î±7 nAChR in HUVECs.
- Varenicline-induced migration contributes to atherosclerotic aggravation.
- Varenicline may increase the risk of cardiovascular events.
Varenicline is a widely used and effective drug for smoking cessation. Despite its efficacy, varenicline increases the risk of cardiovascular disease. We previously demonstrated that varenicline aggravates atherosclerotic plaque formation in apolipoprotein E knockout mice. However, little is known about its effects in vascular endothelial cells. Therefore, we examined whether varenicline promotes migration of human umbilical vein endothelial cells (HUVECs) using the Boyden chamber assay. Varenicline (100Â Î¼M) markedly promoted migration of HUVECs and decreased expression of vascular endothelial (VE)-cadherin, an endothelial adhesion molecule. Extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK) signaling were markedly activated by varenicline. Methyllycaconitine (MLA; 100Â nM), an Î±7 nicotinic acetylcholine receptor (nAChR) antagonist, but not dihydro-Î²-erythroidine hydrobromide (DHÎ²E; 20Â Î¼M) blocked varenicline-stimulated migration and varenicline-activated ERK, p38 and JNK signaling in HUVECs. MLA (100Â nM), PD98059 (an ERK inhibitor; 20Â Î¼M), SB203580 (a p38 inhibitor; 20Â Î¼M) and SP600125 (a JNK inhibitor; 20Â Î¼M) also blocked cell migration and varenicline-induced downregulation of VE-cadherin expression in HUVECs. These findings suggest that varenicline promotes HUVEC migration by lowering VE-cadherin expression due to activated ERK/p38/JNK signaling through Î±7 nAChR. These processes probably contribute to varenicline-aggravated atherosclerotic plaque. Hence, an increased risk of cardiovascular events upon varenicline treatment might occur and must be considered in patients with cardiovascular diseases.
Journal: Toxicology - Volume 390, 1 September 2017, Pages 1-9