ArticleJournal of the American Heart Association2022
Wnt Site Signaling Inhibitor Secreted Frizzled-Related Protein 3 Protects Mitral Valve Endothelium From Myocardial Infarction-Induced Endothelial-to-Mesenchymal Transition.
Article in Journal of the American Heart Association, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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
16 citing papers in PubMed, 18 citations in OpenAlex.
- SGLT2 inhibitors: mechanisms, physiology and pharmacology, and clinical applications.Molecular biomedicine · 2026Review
- Valvular Leaflets Are Not Innocent Bystanders: Divergent Fibrotic Remodeling Accompanies Functional Mitral and Tricuspid Regurgitation.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Endothelial to mesenchymal transition in cardiovascular diseases: molecular insights and clinical perspectives.European heart journal · 2026Review
- Review
- Endothelial-to-mesenchymal transition in the central nervous system: A potential therapeutic target to combat age-related vascular fragility.The Journal of pharmacology and experimental therapeutics · 2025Review
- Molecular mechanisms of endothelial-mesenchymal transition and its pathophysiological feature in cerebrovascular disease.Cell & bioscience · 2025Review
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Follicle-stimulating hormone promotes EndMT in endothelial cells by upregulating ALKBH5 expression.Cellular & molecular biology letters · 2025Article
- Linc-ROR Modulates the Endothelial-Mesenchymal Transition of Endothelial Progenitor Cells through the miR-145/Smad3 Signaling Pathway.Physiological research · 2024Article
- Pathophysiology in Brain Arteriovenous Malformations: Focus on Endothelial Dysfunctions and Endothelial-to-Mesenchymal Transition.Biomedicines · 2024Review
- Endothelial-to-Mesenchymal Transition in Cardiovascular Pathophysiology.International journal of molecular sciences · 2024Review
- Challenges and Opportunities in Valvular Heart Disease: From Molecular Mechanisms to the Community.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Endothelial to mesenchymal transition: at the axis of cardiovascular health and disease.Cardiovascular research · 2024Review
- Linagliptin ameliorated cardiac fibrosis and restored cardiomyocyte structure in diabetic mice associated with the suppression of necroptosis.Journal of diabetes investigation · 2023Article
- Epigallocatechin-3-Gallate Attenuates Myocardial Dysfunction via Inhibition of Endothelial-to-Mesenchymal Transition.Antioxidants (Basel, Switzerland) · 2023Article
- CD45 Is Sufficient to Initiate Endothelial-to-Mesenchymal Transition in Human Endothelial Cells-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
Background The onset and mechanisms of endothelial-to-mesenchymal transition (EndMT) in mitral valve (MV) leaflets following myocardial infarction (MI) are unknown, yet these events are closely linked to stiffening of leaflets and development of ischemic mitral regurgitation. We investigated whether circulating molecules present in plasma within days after MI incite EndMT in MV leaflets. Methods and Results We examined the onset of EndMT in MV leaflets from 9 sheep with inferior MI, 8 with sham surgery, and 6 naïve controls. Ovine MVs 8 to 10 days after inferior MI displayed EndMT, shown by increased vascular endothelial cadherin/α-smooth muscle actin-positive cells. The effect of plasma on EndMT in MV endothelial cells (VECs) was assessed by quantitative polymerase chain reaction, migration assays, and immunofluorescence. In vitro, post-MI plasma induced EndMT marker expression and enhanced migration of mitral VECs; sham plasma did not. Analysis of sham versus post-MI plasma revealed a significant drop in the Wnt signaling antagonist sFRP3 (secreted frizzled-related protein 3) in post-MI plasma. Addition of recombinant sFRP3 to post-MI plasma reversed its EndMT-inducing effect on mitral VECs. RNA-sequencing analysis of mitral VECs exposed to post-MI plasma showed upregulated FOXM1 (forkhead box M1). Blocking FOXM1 reduced EndMT transcripts in mitral VECs treated with post-MI plasma. Finally, FOXM1 induced by post-MI plasma was downregulated by sFRP3. Conclusions Reduced sFRP3 in post-MI plasma facilitates EndMT in mitral VECs by increasing the transcription factor FOXM1. Restoring sFRP3 levels or inhibiting FOXM1 soon after MI may provide a novel strategy to modulate EndMT in the MV to prevent ischemic mitral regurgitation and heart failure.
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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.