Integrated Proteomics and Metabolomics Analysis Reveals Differential Lipid Metabolism in HUVEC under high and low shear stress

ABSTRACT:

OBJECTIVE: Atherosclerotic plaque development is closely associated with the hemodynamic forces applied to endothelial cells (EC). Among these, shear stress (SS) plays a key role in disease development since changes in flow intensity and direction could stimulate an atheroprone or atheroprotective phenotype. EC under low or oscillatory SS (LSS) shows upregulation of inflammatory, adhesion and cellular permeability molecules. On the contrary, cells under high or laminar SS (HSS) increase their expression of protective and anti-inflammatory factors. The mechanism behind SS regulation of an atheroprotective phenotype is not completely elucidated.

APPROACH and RESULTS: Here we used proteomics and metabolomics to better understand the changes in endothelial cells (HUVECs) under in vitro LSS and HSS that promote an atheroprone or atheroprotective profile and how these modifications can be connected to atherosclerosis development. Our data showed that lipid metabolism, in special cholesterol metabolism, was downregulated in cells under LSS. The LDLR showed significant alterations both at the quantitative expression level, as well as regarding post-translational modifications. Under LSS, LDLR was seen at lower concentrations and with a different glycosylation profile. Finally, modulating LDLR with atorvastatin led to the recapitulation of a HSS metabolic phenotype in EC under LSS.

CONCLUSIONS: Altogether, our data suggest that there is significant modulation of lipid metabolism in endothelial cells under different SS intensities and that this could contribute to the atheroprone phenotype of LSS. Statin treatment was able to partially recover the protective profile of these cells.

INSTRUMENT(S): Gas Chromatography MS - Positive (GC-MS (Positive))

SUBMITTER: Gabriela Venturini 

PROVIDER: MTBLS739 | MetaboLights | 2019-07-25

REPOSITORIES: MetaboLights