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

Area of Science:

• Cardiovascular Biology
• Cellular Mechanisms of Atherosclerosis
• Molecular Signaling Pathways

Background:

• Apelin and its receptor (APJ) are expressed in monocytes (MCs) and human umbilical vein endothelial cells (HUVECs).
• Apelin-13 has been previously shown to promote MCs-HUVECs adhesion, a key process in atherosclerosis.
• The precise molecular mechanisms underlying apelin-13-induced MCs-HUVECs adhesion require further elucidation.

Purpose of the Study:

• To investigate the underlying mechanism of apelin-13-induced monocyte-endothelial cell adhesion.
• To explore the roles of reactive oxygen species (ROS) and autophagy in this process.
• To validate findings in an in vivo atherosclerosis model.

Main Methods:

• Assessed ROS generation, NOX4 expression, and autophagy markers (beclin1, LC3-II/I) in HUVECs treated with apelin-13.
• Utilized inhibitors (NAC, catalase, DPI, HCQ) and siRNA to block ROS and autophagy pathways.
• Measured ICAM-1 expression and MCs-HUVECs adhesion.
• Administered apelin-13 to ApoE-/- mice on a high-fat diet (HFD) to assess in vivo effects on atherosclerotic plaque and molecular markers.

Main Results:

• Apelin-13 significantly increased ROS generation, NOX4 expression, and autophagy flux in HUVECs.
• Inhibition of ROS (using NAC, catalase, DPI) or autophagy partially blocked apelin-13-induced adhesion and ICAM-1 expression.
• Rapamycin enhanced adhesion, which was reversed by ROS inhibitors.
• Apelin-13 treatment in ApoE-/- (HFD) mice led to increased atherosclerotic plaque, NOX4, and LC3-II/I expression.

Conclusions:

• Apelin-13 induces monocyte-endothelial cell adhesion through a pathway involving ROS generation and subsequent autophagy activation.
• The ROS-autophagy axis plays a critical role in apelin-13-mediated endothelial cell activation and adhesion.
• Targeting this pathway may offer therapeutic strategies for atherosclerosis.