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Comparative transcriptomic analysis of circulating endothelial cells in sickle cell stroke.
Júlia Nicoliello Pereira de Castro1, Sueli Matilde da Silva Costa1, Ana Carolina Lima Camargo1
1Laboratory of Human Genetics, Center for Molecular Biology and Genetic Engineering-CBMEG, Universidade Estadual de Campinas-UNICAMP, Campinas, São Paulo, 13083-875, Brazil.
Annals of Hematology
|February 22, 2024
Summary
Sickle cell anemia (SCA) patients with ischemic stroke (IS) show altered endothelial cells. Gene expression analysis reveals persistent angiogenic processes, offering potential targets for stroke recovery in SCA.
Area of Science:
- Vascular biology
- Hematology
- Genomics
Background:
- Ischemic stroke (IS) is a major complication of sickle cell anemia (SCA), contributing to significant mortality.
- Vasculopathy in SCA involves rheological changes, altered cell adhesion, inflammation, and endothelial dysfunction.
- The endothelium plays a critical role in ischemia-induced repair and neovascularization.
Purpose of the Study:
- To conduct a comparative transcriptomic analysis of endothelial colony-forming cells (ECFCs) from SCA patients with and without IS.
- To identify differentially expressed genes (DEGs) and understand their biological relevance in the context of IS in SCA.
- To explore potential molecular targets for improving stroke outcomes in SCA.
Main Methods:
- Comparative transcriptomic analysis of ECFCs from SCA patients (with and without IS) and controls.
- Functional enrichment analysis of DEGs.
- Protein-protein interaction (PPI) network construction and in silico prediction of regulatory factors.
Main Results:
- Identified 2469 DEGs between ECFCs from SCA patients with and without IS.
- DEGs are associated with key endothelial cell functions including proliferation, migration, angiogenesis, and defense response.
- Genes like AKT1, E2F1, CDCA5, EGFL7, HRAS, IRF3, and TGFB1 were highlighted for their roles in these pathways.
- Evidence suggests a persistent angiogenic process in ECFCs from IS patients, even long after the event.
Conclusions:
- The study provides novel insights into the molecular mechanisms underlying IS in SCA by analyzing ECFC gene expression.
- Identified DEGs and pathways offer potential molecular targets for therapeutic interventions aimed at stroke outcome improvement in SCA.
- The findings highlight the persistent angiogenic activity in ECFCs from IS patients, contributing to understanding endothelial cell roles in stroke recovery.
