ArticleJournal of molecular and cellular cardiology2015
Reciprocal interactions between mitral valve endothelial and interstitial cells reduce endothelial-to-mesenchymal transition and myofibroblastic activation.
Article in Journal of molecular and cellular cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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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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
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- The Role of Transforming Growth Factor-β Signaling in Myxomatous Mitral Valve Degeneration.Frontiers in cardiovascular medicine · 2022Pooled it
- SNAI2/SLUG: a key regulator of endothelial-to-mesenchymal transition and vascular remodeling in cardiovascular diseases.Journal of cardiothoracic surgery · 2026Review
- Inflammatory and hormonal crosstalk linking rheumatic fever to chronic valvular heart disease.Molecular biology reports · 2026Review
- Plasma aldosterone concentration and valvular heart disease in hypertensive patients: a large cross-sectional study.Scientific reports · 2026Article
- Valve biology and rheumatic heart disease pathogenesis.Nature cardiovascular research · 2026Review
- Active endothelial and neural regulation of valve biology, health, and disease.Frontiers in cardiovascular medicine · 2026Review
- Mechanisms of mitral valve development and disease.Frontiers in cardiovascular medicine · 2026Review
- Chronic Mitral Valve Fibrosis in Rheumatic Heart Disease: From Immune Trigger to Inflammatory and Mechanical Progression.Journal of the American Heart Association · 2025Review
- Reconceptualizing Endothelial-to-mesenchymal transition in atherosclerosis: Signaling pathways and prospective targeting strategies.Journal of advanced research · 2025Review
- Unveiling the Angiogenic Potential and Functional Decline of Valve Interstitial Cells During Calcific Aortic Valve Stenosis Progression.Journal of cellular and molecular medicine · 2025Article
- Lineage Tracing Identifies Dynamic Contribution of Endothelial Cells to Cardiac Valve Mesenchyme During Development.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2023Article
- CD45 Is Sufficient to Initiate Endothelial-to-Mesenchymal Transition in Human Endothelial Cells-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Genetics and pathophysiology of mitral valve prolapse.Frontiers in cardiovascular medicine · 2023Review
- Biology of mitral valve prolapse: from general mechanisms to advanced molecular patterns-a narrative review.Frontiers in cardiovascular medicine · 2023Review
- The Haemodynamic and Pathophysiological Mechanisms of Calcific Aortic Valve Disease.Biomedicines · 2022Review
- Perspectives on pediatric congenital aortic valve stenosis: Extracellular matrix proteins, post translational modifications, and proteomic strategies.Frontiers in cardiovascular medicine · 2022Review
- Uncoupling the Vicious Cycle of Mechanical Stress and Inflammation in Calcific Aortic Valve Disease.Frontiers in cardiovascular medicine · 2022Review
- Valvular Endothelial Cell Response to the Mechanical Environment-A Review.Cell biochemistry and biophysics · 2021Review
- Endothelial-Mesenchymal Transition in Cardiovascular Disease.Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- Tumor necrosis factor alpha and interleukin 1 beta suppress myofibroblast activation via nuclear factor kappa B signaling in 3D-cultured mitral valve interstitial cells.Acta biomaterialia · 2021Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Thickening of mitral leaflets, endothelial-to-mesenchymal transition (EndMT), and activated myofibroblast-like interstitial cells have been observed in ischemic mitral valve regurgitation. We set out to determine if interactions between mitral valve endothelial cells (VECs) and interstitial cells (VICs) might affect these alterations. We used in vitro co-culture in Transwell™ inserts to test the hypothesis that VICs secrete factors that inhibit EndMT and conversely, that VECs secrete factors that mitigate the activation of VICs to a myofibroblast-like, activated phenotype. Primary cultures and clonal populations of ovine mitral VICs and VECs were used. Western blot, quantitative reverse transcriptase PCR (qPCR) and functional assays were used to assess changes in cell phenotype and behavior. VICs or conditioned media from VICs inhibited transforming growth factor β (TGFβ)-induced EndMT in VECs, as indicated by reduced expression of EndMT markers α-smooth muscle actin (α-SMA), Slug, Snai1 and MMP-2 and maintained the ability of VECs to mediate leukocyte adhesion, an important endothelial function. VECs or conditioned media from VECs reversed the spontaneous cell culture-induced change in VICs to an activated phenotype, as indicated by reduced expression of α-SMA and type I collagen, increased expression chondromodulin-1 (Chm1), and reduced contractile activity. These results demonstrate that mitral VECs and VICs secrete soluble factors that can reduce VIC activation and inhibit TGFβ-driven EndMT, respectively. These findings suggest that the endothelium of the mitral valve is critical for the maintenance of a quiescent VIC phenotype and that, in turn, VICs prevent EndMT. We speculate that the disturbance of the ongoing reciprocal interactions between VECs and VICs in vivo may contribute to the thickened and fibrotic leaflets observed in ischemic mitral regurgitation, and in other types of valve 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.