Apelin-13 stimulates angiogenesis by promoting cross‑talk between AMP-activated protein kinase and Akt signaling in myocardial microvascular endothelial cells

Yang,Xiaoman; Zhu,Wei; Zhang,Pu; Chen,Kankai; Zhao,Lijie; Li,Jingbo; Wei,Meng; Liu,Mingya

doi:10.3892/mmr.2014.1984

Apelin-13 stimulates angiogenesis by promoting cross‑talk between AMP-activated protein kinase and Akt signaling in myocardial microvascular endothelial cells

Authors:
- Xiaoman Yang
- Wei Zhu
- Pu Zhang
- Kankai Chen
- Lijie Zhao
- Jingbo Li
- Meng Wei
- Mingya Liu
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Affiliations: Division of Cardiology, Shanghai 6th People's Hospital, Shanghai Jiao Tong University School of Medicine, State Key Discipline Division, Shanghai 200233, P.R. China
Published online on: February 25, 2014 https://doi.org/10.3892/mmr.2014.1984
Pages: 1590-1596

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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.

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