title: Apelin-13 stimulates angiogenesis by promoting cross‑talk between AMP-activated protein kinase and Akt signaling in myocardial microvascular endothelial cells.
abstract: Currently, there is major interest in the functions of apelin-13, an endogenous ligand for the orphan G-protein coupled receptor APJ, a receptor that closely resembles the angiotensin receptor AT1. In the present study, the role of apelin-13 in angiogenesis and its mechanism as a novel angiogenic factor in myocardial microvascular endothelial cells (MMVECs) was investigated. It was revealed that apelin-13 can promote proliferation, migration and tube formation in MMVECs. In addition, apelin-13 dose dependently stimulated the phosphorylation of AMP-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) at Thr-172 and Ser-1179, respectively. The treatment with the AMPK (compound C) and protein kinase Akt/protein kinase B (Akt; LY294002) inhibitor significantly suppressed the apelin‑13-induced AMPK, Akt and eNOS phosphorylation. They also inhibited the apelin13‑stimulated endothelial cell migration and tube formation. Therefore, we hypothesize that apelin-13 promotes angiogenesis through the modulation of AMPK and Akt signaling in MMVECs.
authors.affiliation: Division of Cardiology, Shanghai 6th People's Hospital, Shanghai Jiao Tong University School of Medicine, State Key Discipline Division, Shanghai 200233, P.R. China.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Yang
authors.affiliation: Division of Cardiology, Shanghai 6th People's Hospital, Shanghai Jiao Tong University School of Medicine, State Key Discipline Division, Shanghai 200233, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Division of Cardiology, Shanghai 6th People's Hospital, Shanghai Jiao Tong University School of Medicine, State Key Discipline Division, Shanghai 200233, P.R. China.
authors.forename: Pu
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Division of Cardiology, Shanghai 6th People's Hospital, Shanghai Jiao Tong University School of Medicine, State Key Discipline Division, Shanghai 200233, P.R. China.
authors.forename: Kankai
authors.initials: K
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Shanghai 6th People's Hospital, Shanghai Jiao Tong University School of Medicine, State Key Discipline Division, Shanghai 200233, P.R. China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Division of Cardiology, Shanghai 6th People's Hospital, Shanghai Jiao Tong University School of Medicine, State Key Discipline Division, Shanghai 200233, P.R. China.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Cardiology, Shanghai 6th People's Hospital, Shanghai Jiao Tong University School of Medicine, State Key Discipline Division, Shanghai 200233, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wei
authors.affiliation: Division of Cardiology, Shanghai 6th People's Hospital, Shanghai Jiao Tong University School of Medicine, State Key Discipline Division, Shanghai 200233, P.R. China.
authors.forename: Mingya
authors.initials: M
authors.lastname: Liu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C495199:apelin-13 peptide; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases