ArticleEuropean heart journal2023
Sortilin enhances fibrosis and calcification in aortic valve disease by inducing interstitial cell heterogeneity.
Article in European heart journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 67 citations in OpenAlex.
- Aortic valve disease: Novel animal models for advancing our understanding of the underlying mechanisms.Animal models and experimental medicine · 2026Review
- Spatially Distinct Macrophage Subsets Drive Myofibroblast Heterogeneity and Maladaptive Fibrosis in Lupus Nephritis.bioRxiv : the preprint server for biology · 2026Article
- Contactin-2 protects against aortic valve calcification via osteogenic differentiation inhibition.Scientific reports · 2026Article
- Considerations in the Use of Mouse Models of Vascular and Valvular Calcification.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Age-associated methionine sulfoxide reductase A protects against valvular interstitial cell senescence and valvular calcification.GeroScience · 2026Article
- Construction of a Three-Dimensional Calcific Aortic Valve Disease Model Using Human iPSC-Derived Valvular Interstitial Cells.Stem cell reviews and reports · 2026Article
- The molecular signature of degeneration in explanted decellularized allogeneic heart valves.Frontiers in cardiovascular medicine · 2026Article
- The role of sortilin in cardiovascular calcification: mechanisms and therapeutic potential.Frontiers in cardiovascular medicine · 2026Review
- Article
- The Pathogenic Roles of Local Vitamin D Metabolism Defect in Valve Inflammation and Calcification.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- IGF1-mediated mesenchymal-endothelial transition as a potential regulatory target in calcific aortic valve disease.BMC medicine · 2025Article
- Immune Cell Dynamics in Cardiac Diseases: Insights From Single-Cell Sequencing.Journal of cellular and molecular medicine · 2025Review
- Indoxyl sulfate: fuelling cardiovascular inflammation and calcification.Cardiovascular research · 2025Article
- SORT1 promote the metastasis and invasion of hepatocellular carcinoma via p38/β-catenin/ZEB1 signaling pathway.Cell death & disease · 2025Article
- Antisense Oligonucleotide Targeting Sortilin Reduces Vascular Calcification in Mice in a Sex-Dependent Manner.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Knockdown of PARM1 Alleviates Aortic Valve Calcification via the PRKCH-MAPK Signaling Pathway.JACC. Basic to translational science · 2025Article
- Aortic valve stenosis and osteoporosis: insights from a mouse model.BMC cardiovascular disorders · 2025Article
- Dapagliflozin alleviates mitochondrial damage in the myocardium under diabetic conditions by targeting sortilin.Cellular and molecular life sciences : CMLS · 2025Article
- Navigating the Landscape of Translational Medicine of Calcific Aortic Valve Disease: Bridging Bench to Bedside.JACC. Asia · 2025Review
- Calcific aortic stenosis: omics-based target discovery and therapy development.European heart journal · 2025Review
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Authors and funding
27 authors at 5 institutions in 3 countries.
Funding
Abstract
aimsCalcific aortic valve disease (CAVD) is the most common valve disease, which consists of a chronic interplay of inflammation, fibrosis, and calcification. In this study, sortilin (SORT1) was identified as a novel key player in the pathophysiology of CAVD, and its role in the transformation of valvular interstitial cells (VICs) into pathological phenotypes is explored. METHODS AND
resultsAn aortic valve (AV) wire injury (AVWI) mouse model with sortilin deficiency was used to determine the effects of sortilin on AV stenosis, fibrosis, and calcification. In vitro experiments employed human primary VICs cultured in osteogenic conditions for 7, 14, and 21 days; and processed for imaging, proteomics, and transcriptomics including single-cell RNA-sequencing (scRNA-seq). The AVWI mouse model showed reduced AV fibrosis, calcification, and stenosis in sortilin-deficient mice vs. littermate controls. Protein studies identified the transition of human VICs into a myofibroblast-like phenotype mediated by sortilin. Sortilin loss-of-function decreased in vitro VIC calcification. ScRNA-seq identified 12 differentially expressed cell clusters in human VIC samples, where a novel combined inflammatory myofibroblastic-osteogenic VIC (IMO-VIC) phenotype was detected with increased expression of SORT1, COL1A1, WNT5A, IL-6, and serum amyloid A1. VICs sequenced with sortilin deficiency showed decreased IMO-VIC phenotype.
conclusionSortilin promotes CAVD by mediating valvular fibrosis and calcification, and a newly identified phenotype (IMO-VIC). This is the first study to examine the role of sortilin in valvular calcification and it may render it a therapeutic target to inhibit IMO-VIC emergence by simultaneously reducing inflammation, fibrosis, and calcification, the three key pathological processes underlying CAVD.
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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.