ArticleCardiovascular research2013
Noggin attenuates the osteogenic activation of human valve interstitial cells in aortic valve sclerosis.
Article in Cardiovascular research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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
29 citing papers in PubMed, 52 citations in OpenAlex.
- Orphan Nuclear Receptor NR4A1 Promotes Proliferation and Osteogenic Differentiation of Valvular Interstitial Cells through Activation of CCND2.International journal of biological sciences · 2026Article
- Serotonin transporter downregulation is associated with aortic stenosis, and early profibrotic remodeling is mitigated by pharmacological inhibition of HTR2B receptor.Frontiers in cardiovascular medicine · 2026Article
- Identification of Diagnostic Genes of Aortic Stenosis That Progresses from Aortic Valve Sclerosis.Journal of inflammation research · 2024Article
- Influence of Aortic Valve Stenosis and Wall Shear Stress on Platelets Function.Journal of clinical medicine · 2023Review
- Lipoprotein(a), a Lethal Player in Calcific Aortic Valve Disease.Frontiers in cell and developmental biology · 2022Review
- The mechanistic pathways of oxidative stress in aortic stenosis and clinical implications.Theranostics · 2022Review
- On the role of predicted in vivo mitral valve interstitial cell deformation on its biosynthetic behavior.Biomechanics and modeling in mechanobiology · 2021Article
- On Valve Interstitial Cell Signaling: The Link Between Multiscale Mechanics and Mechanobiology.Cardiovascular engineering and technology · 2021Review
- Disease-inspired tissue engineering: Investigation of cardiovascular pathologies.ACS biomaterials science & engineering · 2020Review
- Circulating and tissue matricellular RNA and protein expression in calcific aortic valve disease.Physiological genomics · 2020Article
- Interstitial cells in calcified aortic valves have reduced differentiation potential and stem cell-like properties.Scientific reports · 2019Article
- Porphyrin-Based SOD Mimic MnTnBu OE -2-PyPJournal of the American Heart Association · 2018Article
- [Role of neuropeptide substance P and the bone morphogenetic protein signaling pathway in osteogenic differentiation of ST2 cells].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2018Article
- Exploiting novel valve interstitial cell lines to study calcific aortic valve disease.Molecular medicine reports · 2018Article
- Serotonin receptor 2B signaling with interstitial cell activation and leaflet remodeling in degenerative mitral regurgitation.Journal of molecular and cellular cardiology · 2018Article
- Cell Sources for Tissue Engineering Strategies to Treat Calcific Valve Disease.Frontiers in cardiovascular medicine · 2018Review
- Valve Interstitial Cells: The Key to Understanding the Pathophysiology of Heart Valve Calcification.Journal of the American Heart Association · 2017Review
- Pyruvate controls the checkpoint inhibitor PD-L1 and suppresses T cell immunity.The Journal of clinical investigation · 2017Article
- Pathophysiology of Aortic Valve Stenosis: Is It Both Fibrocalcific and Sex Specific?Physiology (Bethesda, Md.) · 2017Review
- Role for Galectin-3 in Calcific Aortic Valve Stenosis.Journal of the American Heart Association · 2016Observational
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsAortic valve sclerosis (AVSc) is a hallmark of several cardiovascular conditions ranging from chronic heart failure and myocardial infarction to calcific aortic valve stenosis (AVS). AVSc, present in 25-30% of patients over 65 years of age, is characterized by thickening of the leaflets with marginal effects on the mechanical proprieties of the valve making its presentation asymptomatic. Despite its clinical prevalence, few studies have investigated the pathogenesis of this disease using human AVSc specimens. Here, we investigate in vitro and ex vivo BMP4-mediated transdifferentiation of human valve interstitial cells (VICs) towards an osteogenic-like phenotype in AVSc. METHODS AND
resultsHuman specimens from 60 patients were collected at the time of aortic valve replacement (AVS) or through the heart transplant programme (Controls and AVSc). We show that non-calcified leaflets from AVSc patients can be induced to express markers of osteogenic transdifferentiation and biomineralization through the combinatory effect of BMP4 and mechanical stimulation. We show that BMP4 antagonist Noggin attenuates VIC activation and biomineralization. Additionally, patient-derived VICs were induced to transdifferentiate using either cell culture or a Tissue Engineering (TE) Aortic Valve model. We determine that while BMP4 alone is not sufficient to induce osteogenic transdifferentiation of AVSc-derived cells, the combinatory effect of BMP4 and mechanical stretch induces VIC activation towards a phenotype typical of late calcified stage of the disease.
conclusionThis work demonstrates, for the first time using AVSc specimens, that human sclerotic aortic valves can be induced to express marker of osteogenic-like phenotype typical of advanced severe aortic stenosis.
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