Open AccessIptakalim ameliorates hypoxia‐impaired human endothelial colony‐forming cells proliferation, migration, and angiogenesis via Akt/eNOS pathways
Author(s) -
He Mengyu,
Cui Ting,
Cai Qing,
Wang Hong,
Kong Hui,
Xie Weiping
Publication year - 2019
Publication title -
pulmonary circulation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.791
H-Index - 40
ISSN - 2045-8940
DOI - 10.1177/2045894019875417
Subject(s) - hypoxia (environmental) , enos , protein kinase b , angiogenesis , medicine , nitric oxide synthase type iii , endothelium , nitric oxide , nitric oxide synthase , pharmacology , pulmonary hypertension , endothelial dysfunction , microbiology and biotechnology , cancer research , endothelial stem cell , signal transduction , biology , chemistry , biochemistry , in vitro , organic chemistry , oxygen
Hypoxia‐associated pulmonary hypertension is characterized by pulmonary vascular remodeling. Pulmonary arterial endothelial cells dysfunction is considered as the initial event. As precursor of endothelial cells, endothelial colony‐forming cells (ECFCs) play significant roles in maintenance of endothelium integrity and restoration of normal endothelial cell function. Accumulating data have indicated that hypoxia leads to a decrease in the number and function of ECFCs with defective capacity of endothelial regeneration. Previous studies have reported that the activation of ATP‐sensitive potassium channels (K ATP ) shows therapeutic effects in pulmonary hypertension. However, there have been few reports focusing on the impact of K ATP on ECFC function under hypoxic condition. Therefore, the aim of this study was to investigate whether the opening of K ATP could regulate hypoxia‐induced ECFC dysfunction. Using ECFCs derived from adult peripheral blood, we observed that Iptakalim (Ipt), a novel K ATP opener (KCO), significantly promoted ECFC function including cellular viability, proliferation, migration, angiogenesis, and apoptosis compared with ECFCs exposed to hypoxia. Glibenclamide (Gli), a nonselective K ATP blocker, could eliminate the effects. The protective role of Ipt is attributed to an increased production of nitric oxide (NO), as well as an enhanced activation of angiogenic transduction pathways, containing Akt and endothelial nitric oxide synthase. Our observations demonstrated that K ATP activation could improve ECFC function in hypoxia via Akt/endothelial nitric oxide synthase pathways, which may constitute increase ECFC therapeutic potential for hypoxia‐associated pulmonary hypertension treatment.