ArticleDevelopment (Cambridge, England)2021
Hydrostatic mechanical stress regulates growth and maturation of the atrioventricular valve.
Article in Development (Cambridge, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed, 17 citations in OpenAlex.
- Longitudinal Live Imaging-Derived 4D Hemodynamics and Dynamic Tissue Mechanics Across Outflow Tract Morphogenesis.Annals of biomedical engineering · 2026Article
- Influence of atrial septal defect on mitral valve growth after repair of coarctation of the aorta or an interrupted aortic arch in infants.Clinical and experimental pediatrics · 2026Article
- Compressive stresses in cancer: characterization and implications for tumour progression and treatment.Nature reviews. Cancer · 2024Review
- Early heart development: examining the dynamics of function-form emergence.Biochemical Society transactions · 2024Review
- Differential Development of the Chordae Tendineae and Anterior Leaflet of the Bovine Mitral Valve.Journal of cardiovascular development and disease · 2024Article
- Shear and hydrostatic stress regulate fetal heart valve remodeling through YAP-mediated mechanotransduction.eLife · 2023Article
- Recent advances in quantifying the mechanobiology of cardiac development via computational modeling.Current opinion in biomedical engineering · 2023Article
- Flow-Mediated Factors in the Pathogenesis of Hypoplastic Left Heart Syndrome.Journal of cardiovascular development and disease · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
During valvulogenesis, cytoskeletal, secretory and transcriptional events drive endocardial cushion growth and remodeling into thin fibrous leaflets. Genetic disorders play an important role in understanding valve malformations but only account for a minority of clinical cases. Mechanical forces are ever present, but how they coordinate molecular and cellular decisions remains unclear. In this study, we used osmotic pressure to interrogate how compressive and tensile stresses influence valve growth and shape maturation. We found that compressive stress drives a growth phenotype, whereas tensile stress increases compaction. We identified a mechanically activated switch between valve growth and maturation, by which compression induces cushion growth via BMP-pSMAD1/5, while tension induces maturation via pSer-19-mediated MLC2 contractility. The compressive stress acts through BMP signaling to increase cell proliferation and decrease cell contractility, and MEK-ERK is essential for both compressive stress and BMP mediation of compaction. We further showed that the effects of osmotic stress are conserved through the condensation and elongation stages of development. Together, our results demonstrate that compressive/tensile stress regulation of BMP-pSMAD1/5 and MLC2 contractility orchestrates valve growth and remodeling.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.