Comparative transcriptomic analysis of circulating endothelial cells in sickle cell stroke.

Autor: de Castro JNP; Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering-CBMEG, Universidade Estadual de Campinas-UNICAMP, Campinas, São Paulo, 13083-875, Brazil., da Silva Costa SM; Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering-CBMEG, Universidade Estadual de Campinas-UNICAMP, Campinas, São Paulo, 13083-875, Brazil., Camargo ACL; Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering-CBMEG, Universidade Estadual de Campinas-UNICAMP, Campinas, São Paulo, 13083-875, Brazil., Ito MT; Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering-CBMEG, Universidade Estadual de Campinas-UNICAMP, Campinas, São Paulo, 13083-875, Brazil., de Souza BB; Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering-CBMEG, Universidade Estadual de Campinas-UNICAMP, Campinas, São Paulo, 13083-875, Brazil., de Haidar E Bertozzo V; Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering-CBMEG, Universidade Estadual de Campinas-UNICAMP, Campinas, São Paulo, 13083-875, Brazil., Rodrigues TAR; Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering-CBMEG, Universidade Estadual de Campinas-UNICAMP, Campinas, São Paulo, 13083-875, Brazil., Lanaro C; Hematology and Hemotherapy Center, Universidade Estadual de Campinas-UNICAMP, Campinas, São Paulo, Brazil., de Albuquerque DM; Hematology and Hemotherapy Center, Universidade Estadual de Campinas-UNICAMP, Campinas, São Paulo, Brazil., Saez RC; Hematology and Hemotherapy Center, Universidade Estadual de Campinas-UNICAMP, Campinas, São Paulo, Brazil., Saad STO; Hematology and Hemotherapy Center, Universidade Estadual de Campinas-UNICAMP, Campinas, São Paulo, Brazil., Ozelo MC; Hematology and Hemotherapy Center, Universidade Estadual de Campinas-UNICAMP, Campinas, São Paulo, Brazil., Cendes F; Neuroimaging Laboratory, Department of Neurology, Universidade Estadual de Campinas-UNICAMP, Campinas, São Paulo, Brazil., Costa FF; Hematology and Hemotherapy Center, Universidade Estadual de Campinas-UNICAMP, Campinas, São Paulo, Brazil., de Melo MB; Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering-CBMEG, Universidade Estadual de Campinas-UNICAMP, Campinas, São Paulo, 13083-875, Brazil. melomb@unicamp.br.
Jazyk: angličtina
Zdroj: Annals of hematology [Ann Hematol] 2024 Apr; Vol. 103 (4), pp. 1167-1179. Date of Electronic Publication: 2024 Feb 22.
DOI: 10.1007/s00277-024-05655-6
Abstrakt: Ischemic stroke (IS) is one of the most impairing complications of sickle cell anemia (SCA), responsible for 20% of mortality in patients. Rheological alterations, adhesive properties of sickle reticulocytes, leukocyte adhesion, inflammation and endothelial dysfunction are related to the vasculopathy observed prior to ischemic events. The role of the vascular endothelium in this complex cascade of mechanisms is emphasized, as well as in the process of ischemia-induced repair and neovascularization. The aim of the present study was to perform a comparative transcriptomic analysis of endothelial colony-forming cells (ECFCs) from SCA patients with and without IS. Next, to gain further insights of the biological relevance of differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction network (PPI) construction and in silico prediction of regulatory factors were performed. Among the 2469 DEGs, genes related to cell proliferation (AKT1, E2F1, CDCA5, EGFL7), migration (AKT1, HRAS), angiogenesis (AKT1, EGFL7) and defense response pathways (HRAS, IRF3, TGFB1), important endothelial cell molecular mechanisms in post ischemia repair were identified. Despite the severity of IS in SCA, widely accepted molecular targets are still lacking, especially related to stroke outcome. The comparative analysis of the gene expression profile of ECFCs from IS patients versus controls seems to indicate that there is a persistent angiogenic process even after a long time this complication has occurred. Thus, this is an original study which may lead to new insights into the molecular basis of SCA stroke and contribute to a better understanding of the role of endothelial cells in stroke recovery.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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