Article Impact Level: HIGH Data Quality: STRONG Summary of Angiogenesis. https://doi.org/10.1007/s10456-024-09933-9 Dr. Alexander Brückner et al.
Points
- The study utilized a refined version of the “Häutchen method” to isolate endothelial cells (ECs) from specific regions of the mouse aorta, enhancing the understanding of spatial heterogeneity and its role in aortic aneurysm development.
- Significant differences in gene expression were observed between ECs from aneurysm-prone areas and non-predilection sites in healthy mice, particularly in genes related to extracellular matrix remodeling, angiogenesis, and inflammation.
- ECs from aneurysm-prone areas displayed increased cortical stiffness, suggesting a structural vulnerability that may predispose these regions to aneurysm formation.
- Comparison of ECs from the AngII ApoE−/− mouse model (prone to aneurysms) with sham-operated controls showed that gene expression patterns in diseased mice mirrored those at predilection sites in healthy mice, indicating a consistent genetic response to aneurysm-inducing conditions.
- The findings highlight the importance of regional differences in endothelial cells and suggest potential therapeutic targets to prevent or mitigate site-specific aneurysm development in vascular diseases.
Summary
The study introduced a refined version of the “Häutchen method” tailored for isolating endothelial cells (ECs) from specific sites on the mouse aorta, enabling an in-depth analysis of their spatial heterogeneity and implications in site-specific aortic aneurysm development. By comparing ECs from aneurysm-prone areas of healthy mice to those from adjacent non-predilection sites, the researchers identified significant differences in gene regulation linked to critical biological processes such as extracellular matrix remodeling, angiogenesis, and inflammation—all vital to aneurysm formation. Additionally, ECs at predilection sites exhibited increased cortical stiffness, suggesting a structural predisposition to aneurysm development at these locations.
Further insights were gained by analyzing ECs from the AngII ApoE−/− mouse model, known for its susceptibility to aneurysms. The gene expression profiles of ECs from these diseased mice were compared to sham-operated controls, revealing that the expression patterns in diseased models closely mirrored those observed at the predilection sites in healthy mice. This similarity underscores a genetic consistency in the response of aortic ECs to aneurysm-inducing conditions, reinforcing the role of these cellular mechanisms in the localized onset of the disease.
This research underscores the critical role of regional heterogeneity in aortic endothelial cells and their contribution to site-specific aneurysm development in mice. The modified “Häutchen method” effectively isolates and analyzes ECs at precise locations, facilitating a better understanding of the genetic and functional disparities predisposing certain aortic segments to aneurysms. These findings highlight potential targets for therapeutic intervention, aiming to modulate these critical pathways before they lead to life-threatening vascular ruptures.
Link to the article: https://link.springer.com/article/10.1007/s10456-024-09933-9
References Brückner, A., Brandtner, A., Rieck, S., Matthey, M., Geisen, C., Fels, B., Stei, M., Kusche-Vihrog, K., Fleischmann, B. K., & Wenzel, D. (2024). Site-specific genetic and functional signatures of aortic endothelial cells at aneurysm predilection sites in healthy and AngII ApoE−/− mice. Angiogenesis. https://doi.org/10.1007/s10456-024-09933-9
