Integrated proteomics and metabolomics analysis reveals differential lipid metabolism in human umbilical vein endothelial cells under high and low shear stress

Imagem de Miniatura
Arquivos
art_VENTURINI_Integrated_proteomics_and_metabolomics_analysis_reveals_differential_lipid_2019.PDF (2.01 MB)
Citações na Scopus
22
Tipo de produção
article
Data de publicação
2019
Editora
AMER PHYSIOLOGICAL SOC
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
CARVALHO, Valdemir Melechco
CARDOZO, Karina Helena Morais
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, v.317, n.2, p.C326-C338, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Atherosclerotic plaque development is closely associated with the hemodynamic forces applied to endothelial cells (ECs). 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. ECs under low or oscillatory SS (LSS) show 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. Here we used proteomics and metabolomics to better understand the changes in endothelial cells (human umbilical vein endothelial cells) 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 low-density lipoprotein receptor (LDLR) showed significant alterations both at the quantitative expression level as well as regarding posttranslational 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. 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.
Palavras-chave
endothelial cell, lipids and lipoprotein metabolism, shear stress
URI
https://observatorio.fm.usp.br/handle/OPI/33455
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MCP
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/13
Artigos e Materiais de Revistas Científicas - LIM/64
Artigos e Materiais de Revistas Científicas - ODS/03