SARAH VIANA MATTIOLI
Índice h a partir de 2011
1
Projetos de Pesquisa
Unidades Organizacionais
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina
2 resultados
Resultados de Busca
Agora exibindo 1 - 2 de 2
- Integrated systems biology approach identifies gene targets for endothelial dysfunction(2023) PINHEIRO-DE-SOUSA, Iguaracy; FONSECA-ALANIZ, Miriam Helena; GIUDICE, Girolamo; VALADAO, Iuri Cordeiro; MODESTIA, Silvestre Massimo; MATTIOLI, Sarah Viana; ROSA JUNIOR, Ricardo; ZALMAS, Lykourgos-Panagiotis; FANG, Yun; PETSALAKI, Evangelia; KRIEGER, Jose EduardoEndothelial dysfunction (ED) is critical in the development and progression of cardiovascular (CV) disorders, yet effective therapeutic targets for ED remain elusive due to limited understanding of its underlying molecular mechanisms. To address this gap, we employed a systems biology approach to identify potential targets for ED. Our study combined multi omics data integration, with siRNA screening, high content imaging and network analysis to prioritise key ED genes and identify a pro- and anti-ED network. We found 26 genes that, upon silencing, exacerbated the ED phenotypes tested, and network propagation identified a pro-ED network enriched in functions associated with inflammatory responses. Conversely, 31 genes ameliorated ED phenotypes, pointing to potential ED targets, and the respective anti-ED network was enriched in hypoxia, angiogenesis and cancer-related processes. An independent screen with 17 drugs found general agreement with the trends from our siRNA screen and further highlighted DUSP1, IL6 and CCL2 as potential candidates for targeting ED. Overall, our results demonstrate the potential of integrated system biology approaches in discovering disease-specific candidate drug targets for endothelial dysfunction. imageMulti-omics data integration, genetic and pharmacological perturbations, and network analysis on endothelial cells are combined to identify endothelial dysfunction network signatures and prioritise candidate therapeutic targets.Multi-omics data integration of endothelial cells treated with mimics of major cardiovascular disease factors identified 81 putative endothelial dysfunction (ED) genes.Upon siRNA-mediated gene knockdown, 83% of ED gene candidates affected at least one ED phenotype (26 exacerbating and 31 ameliorating the ED phenotypes).The analyses reveal emergent properties of disease networks, distinguishing between adaptation and rewiring for survival and those associated with deregulation that can be targeted for ED treatment.An orthogonal drug screen on treated endothelial cells provided additional support for DUSP1, IL6 and CCL2 as putative targets for ED. Multi-omics data integration, genetic and pharmacological perturbations, and network analysis on endothelial cells are combined to identify endothelial dysfunction network signatures and prioritise candidate therapeutic targets.image
- Missi ng links in preeclampsia cell model systems of endothelial dysfunction(2023) VIANA-MATTIOLI, Sarah; FONSECA-ALANIZ, Miriam Helena; PINHEIRO-DE-SOUSA, Iguaracy; KRIEGER, Jose Eduardo; SANDRIM, Valeria CristinaPreeclampsia, one of the main hypertensive disorders of pregnancy, is associated with circulating factors released by the ischemic placenta accompanied by systemic endothelial dysfunction. The etiology of preeclampsia remains poorly understood although it is associated with high maternal and fetal mortality and increased cardiovascular disease risk. Most cell model systems used for studying endothelial dysfunction have not taken into account hemodynamic physical factors such as shear-stress forces which may prevent extrapolation of cell data to in vivo settings. We overview the role of hemodynamic forces in modulating endothelial cell function and discuss strategies to reproduce this biological characteristic in vitro to improve our understanding of endothelial dysfunction associated with preeclampsia.