Analysis of Syk/PECAM-1 signaling pathway in low shear stress induced atherosclerosis based on ultrasound imaging

• Published in: Computer methods and programs in biomedicine Vol. 201; p. 105953
• Main Authors: Xia, Lianghua, Zhang, Bo, Sun, Yuqing, Chen, Bingguan, Yu, Zuoren
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.04.2021
• Subjects: Animals; Atherosclerosis; Atherosclerosis - diagnostic imaging; Cells, Cultured; Low shear stress; Phosphorylation; Platelet endothelial cell adhesion molecule; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Rats; Signal Transduction; Spleen tyrosine kinases; Stress, Mechanical; Syk Kinase; Ultrasonography; Platelet endothelial cell adhesion molecule; Low shear stress; Spleen tyrosine kinases; Atherosclerosis
• ISSN: 0169-2607; 1872-7565
• DOI: 10.1016/j.cmpb.2021.105953

•The spatial distribution of WSS was generated by CDFI in vivo.•LSS induced inflammatory through PECAM-1/Syk signaling pathway in atherosclerosis.•LSS influenced the morphology of vascular endothelial cells in vivo.•Inhibition of Syk attenuated LSS-induced inflammatory response. Low shear stress (LSS) has been demonstrated to be involved in function of vascular endothelial cells. Here we tested the hypothesis that activation of Syk played an important in LSS-induced atherosclerosis via PECAM-1 signaling pathway. In vitro, primary human umbilical vein endothelial cells (HUVECs) were stimulated with parallel plate flow chamber system for 12h under normal shear stress (NSS, 15dyne/cm2), LSS (5dyne/cm2) and high shear stress (HSS, 25dyne/cm2), respectively, followed by inflammatory response analysis. In vivo, animal models of rat fed atherogenic diet were treated with LSS stimulation by constricting abdominal aorta with a blunted needle (0.6mm in diameter). The spatial distribution of WSS of blood vessels was generated by WSS quantitative analysis software through color Doppler flow imaging with a high-frequency small animal ultrasound system. Small molecule R406, a well-demonstrated Syk inhibitor, was applied to animals as well as HUVEC cells. In vivo, comparison with the control group was performed, the mean value of WSS distribution of blood vessels was lower in LSS model rat. LSS promoted expression of phosphorylated PECAM-1 (p-PECAM-1) and Syk in LSS model rats. Compared with control group, endothelial cells of the abdominal aorta become less elongated and more polygonal in LSS group, and had a slender shape in LSS with R406 group. In vitro, LSS increased the expression of p-PECAM-1, Syk and NF-κB in HUVECs. Inhibition of Syk attenuated LSS-induced inflammatory response. Activation of Syk resulted in LSS-induced inflammatory response via PECAM-1 signaling pathway both in vitro and in vivo. Syk might be involved in morphological changes of ECs under the influence of LSS.