|  Help  |  About  |  Contact Us

Publication : Low shear stress inhibits endothelial mitophagy via caveolin-1/miR-7-5p/SQSTM1 signaling pathway.

First Author  Liu W Year  2022
Journal  Atherosclerosis Volume  356
Pages  9-17 PubMed ID  35952464
Mgi Jnum  J:328486 Mgi Id  MGI:7335672
Doi  10.1016/j.atherosclerosis.2022.07.014 Citation  Liu W, et al. (2022) Low shear stress inhibits endothelial mitophagy via caveolin-1/miR-7-5p/SQSTM1 signaling pathway. Atherosclerosis 356:9-17
abstractText  BACKGROUND AND AIMS: Mitophagy plays a crucial role in mitochondrial homeostasis and is closely associated with endothelial function. However, the mechanism underlying low blood flow shear stress (SS), detrimental cellular stress, regulating endothelial mitophagy is unclear. This study aimed to investigate whether low SS inhibits endothelial mitophagy via caveolin-1 (Cav-1)/miR-7-5p/Sequestosome 1 (SQSTM1) signaling pathway. METHODS: Low SS in vivo modeling was induced using a perivascular SS modifier implanted in the carotid artery of mice. In vitro modeling, low and physiological SS (4 and 15 dyn/cm(2), respectively) were exerted on human aortic endothelial cells using a parallel plate chamber system. RESULTS: Compared with physiological SS, low SS significantly inhibited endothelial mitophagy shown by down-regulation of SQSTM1, PINK1, Parkin, and LC 3II expressions. Deficient mitophagy deteriorated mitochondrial dynamics shown by up-regulation of Mfn1 and Fis1 expression and led to decreases in mitochondrial membrane potential. Cav-1 plays a bridging role in the process of low SS inhibiting mitophagy. The up-regulated miR-7-5p expression induced by low SS was suppressed after Cav-1 was silenced. The results of dual-luciferase reporter assays showed that miR-7-5p targeted inhibiting the SQSTM1 gene. Oxidative stress reaction shown by the elevation of reactive oxygen species and O2(-) and endothelial dysfunction by the decrease in nitric oxide and the increase in macrophage chemoattractant protein-1 were associated with the low SS inhibiting endothelial mitophagy process. CONCLUSIONS: Cav-1/miR-7-5p/SQSTM1 signaling pathway was the mechanism underlying low SS inhibiting endothelial mitophagy that involves mitochondrial homeostasis impairment and endothelial dysfunction.
Quick Links:
 
Quick Links:
 

Expression

Publication --> Expression annotations

 

Other

3 Bio Entities

0 Expression