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

Autor(es)

Venturini, Gabriela ^[1] ; Malagrino, Pamella Araujo ^[1] ; Padilha, Kallyandra ^[1] ; Tanaka, Leonardo Yuji ^[2] ; Laurindo, Francisco Rafael ^[2] ; Dariolli, Rafael ^[1] ; Carvalho, Valdemir Melechco ^[3] ; Morais Cardozo, Karina Helena ^[3] ; Krieger, Jose Eduardo ^[1] ; Pereira, Alexandre da Costa ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Lab Genet & Mol Cardiol, Fac Med FMUSP, Heart Inst InCor, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med FMUSP, Heart Inst InCor, Vasc Biol Lab, Sao Paulo - Brazil

^[3] Fleury Grp, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY; v. 317, n. 2, p. C326-C338, AUG 2019.
• Citações Web of Science: 0

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. (AU)

• Processo FAPESP: 16/02406-2 - Identificação de marcadores proteicos de intensidade de shear stress endotelial
• Beneficiário: Gabriela Venturini da Silva
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 13/13526-0 - Identificação de marcadores proteicos de alterações de Shear Stress
• Beneficiário: Gabriela Venturini da Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/17368-0 - Genômica cardiovascular: mechanismos & novas terapias - CVGen mech2ther
• Beneficiário: José Eduardo Krieger
• Modalidade de apoio: Auxílio à Pesquisa - Temático