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Endothelialized Microfluidics for Studying Microvascular Interactions in Hematologic Diseases
Published on: June 22, 2012
Sickle cell vasoocclusion: heterotypic, multicellular aggregations driven by leukocyte adhesion
1Mount Sinai School of Medicine, Department of Medicine (Hematology), New York, New York 10029, USA. paul.frenette@mssm.edu
Sickle cell disease involves altered blood cells and endothelium, leading to vasoocclusion. Understanding the steps of vasoocclusion, from endothelial activation to cell interactions, offers new therapeutic targets for this illness.
Area of Science:
- Hematology
- Vascular Biology
- Pathophysiology
Background:
- Sickle cell disease (SCD) is characterized by homozygous expression of sickle beta-globin.
- This genetic alteration profoundly impacts blood cell function and the endothelium.
- SCD manifests in a wide spectrum of clinical symptoms due to these cellular and vascular changes.
Purpose of the Study:
- To elucidate the sequential, multistep phenomenon of vasoocclusion in sickle cell disease.
- To identify potential therapeutic targets within the vasoocclusive cascade.
- To explore molecular determinants that mediate vasoocclusion for novel treatment strategies.
Main Methods:
- Utilized intravital microscopy in sickle cell mouse models.
- Analyzed the sequential steps of vasoocclusion.
- Investigated endothelial activation by sickle red blood cells (SSRBCs).
Main Results:
- Vasoocclusion is a complex, sequential process.
- Key steps include endothelial activation by SSRBCs.
- Leukocyte (WBC) adhesion and interactions with SSRBCs contribute to reduced blood flow.
Conclusions:
- Each identified step in vasoocclusion presents a potential therapeutic target.
- Identifying molecular mediators of vasoocclusion is crucial.
- New strategies for preventing and treating SCD can be developed based on these findings.
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