Identification of MEST as a critical player in mechanotransduction of endothelial cells in response to shear stress in atherosclerosis

• Published in: Physiology (Bethesda, Md.) Md.), 2023-05, Vol.38 (S1)
• Main Authors: Zeng, Ye, Fu, Bingmei
• Format: Article
• Language: English
• ISSN: 1548-9213; 1548-9221
• DOI: 10.1152/physiol.2023.38.S1.5732531

Abstract only OBJECTIVE: Atherosclerosis (AS) is a chronic disease characterized by the inflammation and the deposition of cholesterol in arterial intima, which is the common pathological basis of various cardiovascular and cerebrovascular diseases. Fluid shear stress (FSS) is an important regulatory factor of cellular cholesterol metabolism during the occurrence and progression of AS. However, the mechanism by which FSS regulated the deposition of cholesterol in AS remains unclear. METHODS: By using a novel cell model of foaming established by piled vascular endothelial cells, the transcriptome sequencing and the bioinformatics data mining were carried out to screen the key differential genes involved in the foaming of vascular endothelial cells and the FSS mechanotransduction, and then the qRT-PCR validation of them was performed. Also, the levels of the identified molecules in ApoE-/- atherosclerotic mice were detected. Finally, the role of MEST in vascular endothelial cells was explored by BODIPY staining upon MEST knockdown. RESULTS: We identified MEST that regulated by FSS is downregulated in foaming endothelial cells, and is also reduced in the atherosclerotic lesions. MEST might be closely associated with lipid metabolism, vascular endothelial glycocalyx, G protein-coupled receptor signaling, and cell-to-cell communication. Knockdown of MEST induced lipid accumulation in vascular endothelial cells. CONCLUSION: MEST is an antiatherogenic molecule, which might control the endothelial injury and atherogenic initiation. This project was supported by the National Natural Science Foundation of China (12272246). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.