Open AccessActivation of ATP ‐sensitive potassium channels facilitates the function of human endothelial colony‐forming cells via Ca 2+ /Akt/ eNOS pathway
Author(s) -
Wu Yan,
He MengYu,
Ye JianKui,
Ma ShuYing,
Huang Wen,
Wei YongYue,
Kong Hui,
Wang Hong,
Zeng XiaoNing,
Xie WeiPing
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13006
Subject(s) - enos , atp synthase , nicorandil , microbiology and biotechnology , potassium channel , protein kinase b , chemistry , angiogenesis , atp sensitive potassium channel , biochemistry , glibenclamide , biology , signal transduction , nitric oxide synthase , biophysics , medicine , endocrinology , cancer research , enzyme , diabetes mellitus
Accumulating data, including those from our laboratory, have shown that the opening of ATP ‐sensitive potassium channels ( K ATP ) plays a protective role in pulmonary vascular diseases ( PVD ). As maintainers of the endothelial framework, endothelial colony‐forming cells ( ECFC s) are considered excellent candidates for vascular regeneration in cases of PVD . Although K ATP openers ( KCO s) have been demonstrated to have beneficial effects on endothelial cells, the impact of K ATP on ECFC function remains unclear. Herein, this study investigated whether there is a distribution of K ATP in ECFC s and what role K ATP play in ECFC modulation. By human ECFC s isolated from adult peripheral blood, K ATP were confirmed for the first time to express in ECFC s, comprised subunits of Kir (Kir6.1, Kir6.2) and SUR 2b. KCO s such as the classical agent nicorandil (Nico) and the novel agent iptakalim (Ipt) notably improved the function of ECFC s, promoting cell proliferation, migration and angiogenesis, which were abolished by a non‐selective K ATP blocker glibenclamide (Gli). To determine the underlying mechanisms, we investigated the impacts of KCO s on Ca MKII , Akt and endothelial nitric oxide synthase pathways. Enhanced levels were detected by western blotting, which were abrogated by Gli. This suggested an involvement of Ca 2+ signalling in the regulation of ECFC s by K ATP . Our findings demonstrated for the first time that there is a distribution of K ATP in ECFC s and K ATP play a vital role in ECFC function. The present work highlighted a novel profile of K ATP as a potential target for ECFC modulation, which may hold the key to the treatment of PVD .