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Impact of disrupted cyclic stretch in intracranial aneurysms: Insights from endothelial cell transcriptomic dataset
Mannekomba R Diagbouga1, Sylvain Lemeille1,2, Sandrine Morel1,2,3
1Department of Pathology and Immunology, Faculty of Medicine, University of Geneva. Rue Michel-Servet 1, 1211 Geneva, Switzerland.
Insights
Cyclic circumferential stretch (CCS) influences endothelial cell function in intracranial aneurysms (IAs). Understanding this mechanical force
Area of Science:
- Vascular Biology
- Biomedical Engineering
- Genomics
Background:
- Intracranial aneurysms (IAs) rupture causing hemorrhagic stroke, with current treatments having elevated complication rates.
- Existing treatments for IAs do not guarantee prevention of growth or rupture.
- Understanding cellular and molecular mechanisms is crucial for developing new IA treatments.
Purpose of the Study:
- To investigate the effect of aneurysmal cyclic circumferential stretch (CCS) on endothelial cell (EC) function.
- To explore the potential significance of CCS in intracranial aneurysm (IA) disease progression and wall remodeling.
- To analyze gene expression changes in ECs under different CCS conditions.
Main Methods:
- Generated RNA-sequencing (RNA-seq) data from human umbilical vein endothelial cells (HUVECs).
- Exposed HUVECs to physiological (6%) and aneurysmal (static) CCS conditions.
- Performed differential gene expression and pathway enrichment analyses, focusing on cell junction genes.
Main Results:
- Identified significant gene expression differences between HUVECs exposed to static versus 6% CCS.
- Pathway analysis revealed altered cellular functions in response to varying mechanical stretch.
- Highlighted differential expression of cell junction genes, suggesting an impact on endothelial stability.
Conclusions:
- Cyclic circumferential stretch (CCS) significantly impacts endothelial cell (EC) function and gene expression.
- Findings suggest CCS plays a role in the cellular and molecular mechanisms of intracranial aneurysm (IA) disease.
- The generated transcriptomic profile provides valuable insights for understanding EC mechanobiology in vascular diseases.
Abstract:
Intracranial aneurysm (IA) rupture is a common cause of hemorrhagic stroke. The treatment of unruptured IAs is a challenging decision that requires delicate risk stratification. The rate of poor clinical outcomes after surgical intervention (aneurysm clipping) or endovascular coiling remains elevated (6.7% and 4.8%, respectively), and they do not provide an absolute guarantee to prevent IA growth and rupture. Currently, there is no pharmaceutical treatment to cure or stabilize IAs. Improving the current or developing new treatments for IA disease would require a better understanding of the cellular and molecular mechanisms occurring in the different stages of the disease. Hemodynamic forces play a critical role in IA disease. While the role of wall shear stress in IAs is well-established, the influence of cyclic circumferential stretch (CCS) still needs clarification. IAs are generally characterized by a lack of CCS. In this investigation, we sought to understand the effect of aneurysmal CCS on endothelial cell (EC) function and its potential significance in IA disease, hypothesizing that CCS can influence IA wall remodelling. RNA-seq data were generated from human umbilical vein ECs (HUVECs) exposed to physiological (6%) or aneurysmal CCS (static). We performed differential gene expression and pathway enrichment analysis. Additionally, we highlighted cell junction gene expression between static and 6% CCS to contribute to the debate about how cell junctions affect endothelium stability and integrity. Researchers in the vascular biology field may benefit from this transcriptomic profile to understand the effect of mechanical stretch on EC biology and its potential significance in vascular disease development.
