MIRIAM HELENA FONSECA ALANIZ
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
- Uncovering emergent phenotypes in endothelial cells by clustering of surrogates of cardiovascular risk factors(2022) PINHEIRO-DE-SOUSA, Iguaracy; FONSECA-ALANIZ, Miriam H.; TEIXEIRA, Samantha K.; V, Mariliza Rodrigues; KRIEGER, Jose E.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.
- Multicellular regulation of miR-196a-5p and miR-425-5 from adipose stem cell-derived exosomes and cardiac repair(2022) OLIVEIRA, N. C. de Almeida; NERI, E. A.; SILVA, C. M.; VALADãO, I. C.; FONSECA-ALANIZ, M. H.; ZOGBI, C.; LEVY, D.; BYDLOWSKI, S. P.; KRIEGER, J. E.Cardiac transplantation of adipose-derived stem cells (ASC) modulates the post-myocardial infarction (post-MI) repair response. Biomolecules secreted or shuttled within extracellular vesicles, such as exosomes, may participate in the concerted response. We investigated the exosome’s microRNAs due to their capacity to fine-tune gene expression, potentially affecting the multicellular repair response. We profiled and quantified rat ASC-exosome miRNAs and used bioinformatics to select uncharacterized miRNAs down-regulated in post-MI related to cardiac repair. We selected and validated miR-196a-5p and miR-425-5p as candidates for the concerted response in neonatal cardiomyocytes, cardiac fibroblasts, endothelial cells, and macrophages using a high-content screening platform. Both miRNAs prevented cardiomyocyte ischemia-induced mitochondrial dysfunction and reactive oxygen species production, increased angiogenesis, and polarized macrophages toward the anti-inflammatory M2 immunophenotype. Moreover, miR-196a-5p reduced and reversed myofibroblast activation and decreased collagen expression. Our data provide evidence that the exosome-derived miR-196a-5p and miR-425-5p influence biological processes critical to the concerted multicellular repair response post-MI. © 2022 The Author(s).