title: Involvement of Kv1.5 protein in oxidative vascular endothelial cell injury.
abstract: Endothelial injury related to oxidative stress is a key event in cardiovascular diseases, such as hypertension and atherosclerosis. The activation of the redox-sensitive Kv1.5 potassium channel mediates mitochondrial reactive oxygen species (ROS)-induced apoptosis in vascular smooth muscle cells and some cancer cells. Kv1.5 channel is therefore taken as a new potential therapeutic target for pulmonary hypertension and cancers. Although Kv1.5 is abundantly expressed in vascular endothelium, there is little knowledge of its role in endothelial injury related to oxidative stress. We found that DPO-1, a specific inhibitor of Kv1.5, attenuated H(2)O(2)-evoked endothelial cell apoptosis in an in vivo rat carotid arterial model. In human umbilical vein endothelial cells (HUVECs) and human pulmonary arterial endothelial cells (HPAECs), angiotensin II and oxLDL time- or concentration-dependently enhanced Kv1.5 protein expression in parallel with the production of intracellular ROS and endothelial cell injury. Moreover, siRNA-mediated knockdown of Kv1.5 attenuated, whereas adenovirus-mediated Kv1.5 cDNA overexpression enhanced oxLDL-induced cellular damage, NADPH oxidase and mitochondria-derived ROS production and restored the decrease in protein expression of mitochondria uncoupling protein 2 (UCP2). Collectively, these data suggest that Kv1.5 may play an important role in oxidative vascular endothelial injury.
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou, P R China.
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Chen
authors.forename: Xiong-Qing
authors.initials: XQ
authors.lastname: Huang
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Zhao
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.forename: Yun-Ying
authors.initials: YY
authors.lastname: Huang
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Guan-Lei
authors.initials: GL
authors.lastname: Wang
authors.forename: Yong-Yuan
authors.initials: YY
authors.lastname: Guan
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002339:Carotid Arteries / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D007473:Ion Channels / Q000378:metabolism; D051666:Kv1.5 Potassium Channel / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism; D018384:Oxidative Stress; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D000071246:Uncoupling Protein 2
chemical_list: D007473:Ion Channels; C496981:KCNA5 protein, human; D051666:Kv1.5 Potassium Channel; D008077:Lipoproteins, LDL; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C000604389:UCP2 protein, human; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; C099252:oxidized low density lipoprotein; D006861:Hydrogen Peroxide