ArticleProceedings of the National Academy of Sciences of the United States of America2011
Cyclic strain induces dual-mode endothelial-mesenchymal transformation of the cardiac valve.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 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.
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Who cites it
88 citing papers in PubMed, 173 citations in OpenAlex.
- Vein graft failure: Pathophysiology, detection, prevention and emerging therapeutic strategies.Pharmacological reviews · 2026Review
- Longitudinal Live Imaging-Derived 4D Hemodynamics and Dynamic Tissue Mechanics Across Outflow Tract Morphogenesis.Annals of biomedical engineering · 2026Article
- Endothelial to mesenchymal transition in cardiovascular diseases: molecular insights and clinical perspectives.European heart journal · 2026Review
- Active endothelial and neural regulation of valve biology, health, and disease.Frontiers in cardiovascular medicine · 2026Review
- Vascular endothelial integration of multiple biophysical stimuli.Frontiers in cardiovascular medicine · 2026Article
- IGF1-mediated mesenchymal-endothelial transition as a potential regulatory target in calcific aortic valve disease.BMC medicine · 2025Article
- Unveiling the intricacies of cardiac valve pathophysiology.Frontiers in cardiovascular medicine · 2025Review
- Towards a more objective and high-throughput spheroid invasion assay quantification method.Scientific reports · 2024Article
- Exercise Induced Endothelial Mesenchymal Transition (EndMT) Facilitates Meniscal Fibrocartilage Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Towards a More Objective and High-throughput Spheroid Invasion Assay Quantification Method.bioRxiv : the preprint server for biology · 2024Article
- Quantified planar collagen distribution in healthy and degenerative mitral valve: biomechanical and clinical implications.Scientific reports · 2024Article
- Endothelial-to-mesenchymal transition in tumour progression and its potential roles in tumour therapy.Annals of medicine · 2023Review
- Palmdelphin Deficiency Evokes NF-κB Signaling in Valvular Endothelial Cells and Aggravates Aortic Valvular Remodeling.JACC. Basic to translational science · 2023Article
- Parametric optimization of culture chamber for cell mechanobiology research.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Challenges of aortic valve tissue culture - maintenance of viability and extracellular matrix in the pulsatile dynamic microphysiological system.Journal of biological engineering · 2023Article
- Utilization of Engineering Advances for Detailed Biomechanical Characterization of the Mitral-Ventricular Relationship to Optimize Repair Strategies: A Comprehensive Review.Bioengineering (Basel, Switzerland) · 2023Review
- Designing Biocompatible Tissue Engineered Heart Valves In Situ: JACC Review Topic of the Week.Journal of the American College of Cardiology · 2023Review
- Human pluripotent stem cell-derived cardiomyocytes align under cyclic strain when guided by cardiac fibroblasts.APL bioengineering · 2022Article
- Integrin-Linked Kinase Expression in Human Valve Endothelial Cells Plays a Protective Role in Calcific Aortic Valve Disease.Antioxidants (Basel, Switzerland) · 2022Article
- The Haemodynamic and Pathophysiological Mechanisms of Calcific Aortic Valve Disease.Biomedicines · 2022Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Endothelial-mesenchymal transformation (EMT) is a critical event for the embryonic morphogenesis of cardiac valves. Inducers of EMT during valvulogenesis include VEGF, TGF-β1, and wnt/β-catenin (where wnt refers to the wingless-type mammary tumor virus integration site family of proteins), that are regulated in a spatiotemporal manner. EMT has also been observed in diseased, strain-overloaded valve leaflets, suggesting a regulatory role for mechanical strain. Although the preponderance of studies have focused on the role of soluble mitogens, we asked if the valve tissue microenvironment contributed to EMT. To recapitulate these microenvironments in a controlled, in vitro environment, we engineered 2D valve endothelium from sheep valve endothelial cells, using microcontact printing to mimic the regions of isotropy and anisotropy of the leaflet, and applied cyclic mechanical strain in an attempt to induce EMT. We measured EMT in response to both low (10%) and high strain (20%), where low-strain EMT occurred via increased TGF-β1 signaling and high strain via increased wnt/β-catenin signaling, suggesting dual strain-dependent routes to distinguish EMT in healthy versus diseased valve tissue. The effect was also directionally dependent, where cyclic strain applied orthogonal to axis of the engineered valve endothelium alignment resulted in severe disruption of cell microarchitecture and greater EMT. Once transformed, these tissues exhibited increased contractility in the presence of endothelin-1 and larger basal mechanical tone in a unique assay developed to measure the contractile tone of the engineered valve tissues. This finding is important, because it implies that the functional properties of the valve are sensitive to EMT. Our results suggest that cyclic mechanical strain regulates EMT in a strain magnitude and directionally dependent manner.
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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.