Apelin-13 attenuates high glucose-induced calcification of MOVAS cells by regulating MAPKs and PI3K/AKT pathways and ROS-mediated signals - 18/06/20
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Graphical abstract |
High glucose induced vascular calcification by triggering ROS-mediated DNA damage and dysfunction of MAPKs and AKT pathways. Apelin-13 significantly attenuated high glucose-induced vascular calcification by inhibiting ROS-mediated DNA damage and regulating of MAPKs and AKT pathways.
Abstract |
Vascular calcification (VC) is an inducement of many cardiovascular diseases. Clinic evidences have confirmed that diabetes was the independent risk factor for VC, and the mechanism has not been well explored. Apelin as a ligand molecule is widely found in the cardiovascular system and showed potential in inhibiting VC, but the inhibitory effect and mechanism of apelin-13 against high glucose-induced VC have not been investigated yet. Herein, apelin-13 was employed to inhibit high glucose-induced VC in mouse aortic vascular smooth muscle cells (MOVAS), and the underlying mechanism was explored. The results showed that apelin-13 significantly inhibited high glucose-induced cells proliferation, migration and invasion of MOVAS cells. Apelin-13 also effectively attenuated high glucose-induced calcification by inhibiting alkaline phosphatase (ALP) activity and expression. Further investigation revealed that apelin-13 dramatically suppressed high glucose-induced DNA damage through inhibiting reactive oxide species (ROS) generation. Moreover, apelin-13 also effectively improved high glucose-induced dysfunction of MAPKs and PI3K/AKT. Inhibition of ERK by inhibitor (U0126) significantly blocked high glucose-induced calcification, which further confirmed the significance of MAPKs. Taken together, these results suggested that apelin-13 had the potential to attenuate high glucose-induced calcification of MOVAS cells by inhibiting ROS-mediated DNA damage and regulating MAPKs and PI3K/AKT pathways. Our findings validated the strategy of using apelin-13 maybe a novel way in treating high glucose-mediated VC.
Le texte complet de cet article est disponible en PDF.Keywords : Vascular calcification, Apelin-13, Alkaline phosphatase, ROS
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