ArticleJournal of molecular and cellular cardiology2016
Growth and maturation of heart valves leads to changes in endothelial cell distribution, impaired function, decreased metabolism and reduced cell proliferation.
Article in Journal of molecular and cellular cardiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 38 citations in OpenAlex.
- Mechanisms and emerging research trends of angiogenesis promotion by small extracellular vesicles from different cellular sources in alleviating myocardial infarction injury.Frontiers in pharmacology · 2026Review
- Healthy ageing in older adults with cardiovascular disease.European heart journal · 2025Review
- Murine Aortic Valve Cell Heterogeneity at Birth.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Article
- The role of endothelial cell-pericyte interactions in vascularization and diseases.Journal of advanced research · 2025Review
- New Insights on the Formation of the Mitral Valve Chordae Tendineae in Fetal Life.Journal of cardiovascular development and disease · 2024Article
- Preservation of human heart valves for replacement in children with heart valve disease: past, present and future.Cell and tissue banking · 2024Review
- Congenital aortic valve stenosis: from pathophysiology to molecular genetics and the need for novel therapeutics.Frontiers in cardiovascular medicine · 2023Review
- Tgfβ1-Cthrc1 Signaling Plays an Important Role in the Short-Term Reparative Response to Heart Valve Endothelial Injury.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Aortic valve cell microenvironment: Considerations for developing a valve-on-chip.Biophysics reviews · 2021Review
- Valvular Endothelial Cell Response to the Mechanical Environment-A Review.Cell biochemistry and biophysics · 2021Review
- Shear type and magnitude affect aortic valve endothelial cell morphology, orientation, and differentiation.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- Isolation of Human Primary Valve Cells for In vitro Disease Modeling.Journal of visualized experiments : JoVE · 2021Article
- PDGFRα: Expression and Function during Mitral Valve Morphogenesis.Journal of cardiovascular development and disease · 2021Article
- Valve endothelial-interstitial interactions drive emergent complex calcific lesion formation in vitro.Biomaterials · 2021Article
- Molecular and Mechanical Mechanisms of Calcification Pathology Induced by Bicuspid Aortic Valve Abnormalities.Frontiers in cardiovascular medicine · 2021Review
- Biology and Biomechanics of the Heart Valve Extracellular Matrix.Journal of cardiovascular development and disease · 2020Review
- The Endocardium and Heart Valves.Cold Spring Harbor perspectives in biology · 2020Review
- Cardiac tissue remodeling in healthy aging: the road to pathology.American journal of physiology. Cell physiology · 2020Review
- MG 53 Protein Protects Aortic Valve Interstitial Cells From Membrane Injury and Fibrocalcific Remodeling.Journal of the American Heart Association · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Risk factors of heart valve disease are well defined and prolonged exposure throughout life leads to degeneration and dysfunction in up to 33% of the population. While aortic valve replacement remains the most common need for cardiovascular surgery particularly in those aged over 65, the underlying mechanisms of progressive deterioration are unknown. In other cardiovascular systems, a decline in endothelial cell integrity and function play a major role in promoting pathological changes, and while similar mechanisms have been speculated in the valves, studies to support this are lacking. The goal of this study was to examine age-related changes in valve endothelial cell (VEC) distribution, morphology, function and transcriptomes during critical stages of valve development (embryonic), growth (postnatal (PN)), maintenance (young adult) and aging (aging adult). Using a combination of in vivo mouse, and in vitro porcine assays we show that VEC function including, nitric oxide bioavailability, metabolism, endothelial-to-mesenchymal potential, membrane self-repair and proliferation decline with age. In addition, density of VEC distribution along the endothelium decreases and this is associated with changes in morphology, decreased cell-cell interactions, and increased permeability. These changes are supported by RNA-seq analysis showing that focal adhesion-, cell cycle-, and oxidative phosphorylation-associated biological processes are negatively impacted by aging. Furthermore, by performing high-throughput analysis we are able to report the differential and common transcriptomes of VECs at each time point that can provide insights into the mechanisms underlying age-related dysfunction. These studies suggest that maturation of heart valves over time is a multifactorial process and this study has identified several key parameters that may contribute to impairment of the valve to maintain critical structure-function relationships; leading to degeneration and disease.
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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.