title: Activation of ATP-sensitive potassium channels facilitates the function of human endothelial colony-forming cells via Ca2+/Akt/eNOS pathway.
abstract: Accumulating data, including those from our laboratory, have shown that the opening of ATP-sensitive potassium channels (KATP) plays a protective role in pulmonary vascular diseases (PVD). As maintainers of the endothelial framework, endothelial colony-forming cells (ECFCs) are considered excellent candidates for vascular regeneration in cases of PVD. Although KATPopeners (KCOs) have been demonstrated to have beneficial effects on endothelial cells, the impact of KATPon ECFC function remains unclear. Herein, this study investigated whether there is a distribution of KATPin ECFCs and what role KATPplay in ECFC modulation. By human ECFCs isolated from adult peripheral blood, KATPwere confirmed for the first time to express in ECFCs, comprised subunits of Kir (Kir6.1, Kir6.2) and SUR2b. KCOs such as the classical agent nicorandil (Nico) and the novel agent iptakalim (Ipt) notably improved the function of ECFCs, promoting cell proliferation, migration and angiogenesis, which were abolished by a non-selective KATPblocker glibenclamide (Gli). To determine the underlying mechanisms, we investigated the impacts of KCOs on CaMKII, Akt and endothelial nitric oxide synthase pathways. Enhanced levels were detected by western blotting, which were abrogated by Gli. This suggested an involvement of Ca2+signalling in the regulation of ECFCs by KATP. Our findings demonstrated for the first time that there is a distribution of KATPin ECFCs and KATPplay a vital role in ECFC function. The present work highlighted a novel profile of KATPas a potential target for ECFC modulation, which may hold the key to the treatment of PVD.
authors.affiliation: Department of Respiratory Medicine, WuXi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Meng-Yu
authors.initials: MY
authors.lastname: He
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Jian-Kui
authors.initials: JK
authors.lastname: Ye
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Shu-Ying
authors.initials: SY
authors.lastname: Ma
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yong-Yue
authors.initials: YY
authors.lastname: Wei
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Kong
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xiao-Ning
authors.initials: XN
authors.lastname: Zeng
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Xie
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D054086:KATP Channels / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D054086:KATP Channels; D015221:Potassium Channels; D000255:Adenosine Triphosphate; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D002118:Calcium
keywords: 
  KATP
  ; Ca2+ signalling; ECFCs; angiogenesis; iptakalim