MiR-137 regulates low-intensity shear stress–induced human aortic endothelial cell apoptosis via JNK/AP-1 signaling

The objective of this study is to evaluate the role of miR-137 in low-intensity shear stress–induced endoplasmic reticulum (ER) stress and cell apoptosis in human aortic endothelial cells (HAECs). HAECs were transfected with miR-137 mimic, miR-137 inhibitor, or the corresponding negative control and then exposed to pulsatile shear stress in a parallel-plate flow chamber at 1, 2, 5, 10, and 15 dyn/cm2 for 3 h. Real-time polymerase chain reaction was used to detect mRNA expression of miR-137 and SDS22. A dual-luciferase reporter assay was employed to verify the direct interaction between miR-137 and SDS22. The internal morphology of cells and cell apoptosis was assessed by TUNEL staining observed under a transmission electron microscope. Meanwhile, the protein expression of oxidative stress–related, apoptosis-related, and activated c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) signaling–related genes were analyzed by western blotting. Low strength shear stress (0–5 dyn/cm2) caused a negative change of HAEC surface and internal morphology in an intensity-dependent manner, and these changes were gradually weakened when shear stress was increased more than 5 dyn/cm2. Furthermore, low-intensity shear stress promoted oxidative stress response, accelerated cell apoptosis, and upregulated miR-137 expression and JNK/AP-1 signaling in HAECs. MiR-137 directly targets SDS22. Knockdown of miR-137 noticeably reduced activation of JNK/AP-1 signaling, oxidative stress response, and cell apoptosis induced by shear stress. MiR-137 regulated low-intensity shear stress–induced human aortic endothelial cell ER stress and cell apoptosis via JNK/AP-1 signaling.