ncovering emergent phenotypes in endothelial cells by clustering of surrogates of cardiovascular risk factor

Autor(es)

Pinheiro-de-Sousa, Iguaracy ^[1] ; Fonseca-Alaniz, Miriam H. ^[1] ; Teixeira, Samantha K. ^[1] ; Rodrigues, V, Mariliza ; Krieger, Jose E. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo HCFMUSP, Hosp Clin, Fac Med, Inst Coracao InCor, Lab Genet & Cardiol Mol, Sao Paulo, SP - Brazil

^[2] Rodrigues, Mariliza, V, Univ Sao Paulo HCFMUSP, Hosp Clin, Fac Med, Inst Coracao InCor, Lab Genet & Cardiol Mol, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 12, n. 1 JAN 25 2022.
• Citações Web of Science: 0

Resumo

Endothelial dysfunction (ED) is a hallmark of atherosclerosis and is influenced by well-defined risk factors, including hypoxia, dyslipidemia, inflammation, and oscillatory flow. However, the individual and combined contributions to the molecular underpinnings of ED remain elusive. We used global gene expression in human coronary artery endothelial cells to identify gene pathways and cellular processes in response to chemical hypoxia, oxidized lipids, IL-1 beta induced inflammation, oscillatory flow, and these combined stimuli. We found that clustering of the surrogate risk factors differed from the sum of the individual insults that gave rise to emergent phenotypes such as cell proliferation. We validated these observations in samples of human coronary artery atherosclerotic plaques analyzed using single-cell RNA sequencing. Our findings suggest a hierarchical interaction between surrogates of CV risk factors and the advent of emergent phenotypes in response to combined stimulation in endothelial cells that may influence ED. (AU)

• Processo FAPESP: 14/50889-7 - INCT 2014: em Medicina Assistida por Computação Científica (INCT-MACC)
• Beneficiário: José Eduardo Krieger
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/17368-0 - Genômica cardiovascular: mechanismos & novas terapias - CVGen mech2ther
• Beneficiário: José Eduardo Krieger
• Modalidade de apoio: Auxílio à Pesquisa - Temático