Recalibrating vascular malformations and mechanotransduction by pharmacological intervention.
(2022) Journal of Clinical Investigation — Vol. 132, n° 8, p. e160227 [1-3] (2022)
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- Abstract
- Circulation of blood throughout the cardiovascular system results in biomechanical forces that profoundly influence vessel development and maintenance. Fluid shear stress along the inner lining of blood vessels imparts mechanical forces upon vascular cells. Endothelial cells (ECs), which line all blood and lymphatic vessels, are exquisitely equipped to sense mechanical forces and to transduce these stimuli into biochemical signals, which control their proliferation, migration, cytoskeleton organization, and cell-cell adhesion. Vascular malformations can arise when patterns of blood flow change or when vascular cells develop a disturbed response to hemodynamic forces due to genetic mutations. For instance, genetic evidence suggests that mutations causing dysregulated RAS/MAPK and nitric oxide (NO) signaling within vascular cells lead to malformations and dysplasias. The influence of biomechanical cues on genetically vulnerable cells provides a promising therapeutic avenue. Vascular malformations are often incurable, and patients experience lifelong chronic pain, disfigurement, or even premature death. A major obstacle to developing useful therapies is our poor understanding of the molecular underpinnings of these vascular defects. Tangible therapeutic approaches may be based on the novel idea that vascular cell responses to blood flow can be normalized using pharmacological modulation.
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Abdelilah-Seyfried, S., Iruela-Arispe, M. L., Penninger, J. M., Tournier-Lasserve, E., Vikkula, M., & Cleaver, O. (2022). Recalibrating vascular malformations and mechanotransduction by pharmacological intervention. Journal of Clinical Investigation, 132(8), e160227 [1-3]. https://doi.org/10.1172/JCI160227 (Original work published 2022)