Apelin-13 promotes cardiomyocyte hypertrophy via PI3K-Akt-ERK1/2-p70S6K and PI3K-induced autophagy

Abstract

Apelin is highly expressed in rat left ventricular hypertrophy Sprague Dawley rat models, and it plays a crucial role in the cardiovascular system. The aim this study was to clarify whether apelin-13 promotes hypertrophy in H9c2 rat cardiomyocytes and to investigate its underlying mechanism. The cardiomyocyte hypertrophy was observed by measuring the diameter, volume, and protein content of H9c2 cells. The activation of autophagy was evaluated by observing the morphology of autophagosomes by transmission electron microscopy, observing the subcellular localization of LC3 by light microscopy, and detecting the membrane-associated form of LC3 by western blot analysis. The phosphatidylinositol 3-kinase (PI3K) signaling pathway was identified and the proteins expression was detected using western blot analysis. The results revealed that apelin-13 increased the diameter, volume, and protein content of H9c2 cells and promoted the phosphorylation of PI3K, Akt, ERK1/2, and p70S6K. Apelin-13 activated the PI3K-Akt-ERK1/2-p70S6K pathway. PI3K inhibitor LY294002, Akt inhibitor 1701-1, ERK1/2 inhibitor PD98059 attenuated the increase of the cell diameter, volume, protein content induced by apelin-13. Apelin-13 increased the autophagosomes and up-regulated the expressions of beclin 1 and LC3-II/I both transiently and stably. The autophagy inhibitor 3MA ameliorated the increase of cell diameter, volume, and protein content that were induced by apelin-13. These results suggested that apelin-13 promotes H9c2 rat cardiomyocyte hypertrophy via PI3K-Akt-ERK1/2-p70S6K and PI3K-induced autophagy.

ROS‐Autophagy pathway mediates monocytes‐human umbilical vein endothelial cells adhesion induced by apelin‐13

“…We demonstrated that apelin‐13 reduced blood pressure (Li et al, ) and promoted vasodilatation of vascular rings on spontaneously hypertension rat in vitro which was mediated by extracellular signal–regulated kinases 1 and 2 (ERK1/2) (Liu et al, ). Besides, we also reported that apelin‐13 promoted cardiomyocytes (Xie et al, ). Furthermore, apelin‐13 induced lung adenocarcinoma cells proliferation and autophagy via ERK1/2 pathway (Yang et al, ).…”

Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth

“…ERK1/2 signaling has also been implicated in the proliferation and autophagy of lung adenocarcinoma cells when stimulated with apelin [43]. Additionally, apelin-mediated ERK signaling has also been shown to regulate cardiomyocyte hypertrophy and to activate the expression of inflammatory cytokines in microglial cells [44,45]. Our results show that ML221 treatment decreased Mz-ChA-1 tumor expression of p-ERK and t-ERK, indicating that this pathway may become less active with ML221 treatment.…”

Apelin/APJ system: A novel potential therapy target for kidney disease

“…Apelin and APJ are widely expressed in many tissues, such as heart, kidney, and blood vessels (Li et al, ; Liu, Chen, & Chen, ; Lv, Li, & Chen, ; Xie et al, ; Yu et al, ). A large amount of evidence indicates that apelin/APJ system plays an important role cardiovascular system (Barnes, Japp, & Newby, ; Galanth, Hus‐Citharel, Li, & Llorens‐Cortes, ; Tycinska, Lisowska, Musial, & Sobkowicz, ; Yu et al, ).…”