ArticleThe Journal of heart valve disease2014
The role of inorganic pyrophosphate in aortic valve calcification.
Article in The Journal of heart valve disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Association between plasma phosphate/pyrophosphate ratio and computed tomography-derived aortic valve calcification score in an unselected cohort of cardiovascular patients.European heart journal. Cardiovascular Imaging · 2026Article
- Valvular calcification in chronic kidney disease: new insights from recent clinical and preclinical studies.Clinical kidney journal · 2025Article
- Macrophages as key modulators of calcific aortic valve disease.Frontiers in cardiovascular medicine · 2025Review
- Insights into preclinical models of calcific aortic valve disease and their translational potential.Frontiers in cardiovascular medicine · 2025Review
- Improved Reversion of Calcifications in Porcine Aortic Heart Valves Using Elastin-Targeted Nanoparticles.International journal of molecular sciences · 2023Article
- Focusing on the Native Matrix Proteins in Calcific Aortic Valve Stenosis.JACC. Basic to translational science · 2023Review
- Valve Endothelial Cell Exposure to High Levels of Flow Oscillations Exacerbates Valve Interstitial Cell Calcification.Bioengineering (Basel, Switzerland) · 2022Article
- Inorganic Pyrophosphate Deficiency Syndromes and Potential Treatments for Pathologic Tissue Calcification.The American journal of pathology · 2022Review
- Inorganic pyrophosphate is reduced in patients with systemic sclerosis.Rheumatology (Oxford, England) · 2022Article
- TNAP as a therapeutic target for cardiovascular calcification: a discussion of its pleiotropic functions in the body.Cardiovascular research · 2022Review
- Models and Techniques to Study Aortic Valve CalcificationFrontiers in pharmacology · 2022Review
- Organ Culture Model of Aortic Valve Calcification.Frontiers in cardiovascular medicine · 2021Article
- Article
- Pseudoxanthoma Elasticum: An Interesting Model to Evaluate Chronic Kidney Disease-Like Vascular Damage without Renal Disease.Kidney diseases (Basel, Switzerland) · 2020Review
- Nucleotide ecto-enzyme metabolic pattern and spatial distribution in calcific aortic valve disease; its relation to pathological changes and clinical presentation.Clinical research in cardiology : official journal of the German Cardiac Society · 2020Article
- A NovelFrontiers in pharmacology · 2020Article
- Inorganic phosphate-osteogenic induction medium promotes osteogenic differentiation of valvular interstitial cells via the BMP-2/Smad1/5/9 and RhoA/ROCK-1 signaling pathways.American journal of translational research · 2020Article
- Tissue Non-Specific Alkaline Phosphatase and Vascular Calcification: A Potential Therapeutic Target.Current cardiology reviews · 2019Review
- Calcific Aortic Valve Disease: a Developmental Biology Perspective.Current cardiology reports · 2018Review
- Ectopic calcification in pseudoxanthoma elasticum responds to inhibition of tissue-nonspecific alkaline phosphatase.Science translational medicine · 2017Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
background and aim of the studyAortic valve (AV) calcification is a major cause of morbidity and mortality, yet the molecular mechanisms involved are poorly understood. Hence, an ex vivo model of calcification in intact AVs was developed in order to test the role of orthophosphate and pyrophosphate (PPi), both of which factors are known to influence vascular calcification.
methodsPorcine AV leaflets were cultured in serum-free medium under static conditions for eight days, over which time leaflet architecture and viability were preserved. Calcification was measured as the incorporation of 45Ca, with confirmation by Alizarin Red staining.
resultsCalcification required both a high phosphate concentration (3.8 mM) and removal of PPi with alkaline phosphatase or inorganic pyrophosphatase. Calcification occurred predominantly on the fibrosa and was arrested by the bisphosphonate etidronate, a non-hydrolyzable analog of PPi. Leaflets released PPi into the medium, and this was enhanced by MLS38949, a specific inhibitor of tissue non-specific alkaline phosphatase (TNAP). Furthermore, leaflets synthesized PPi from extracellular ATP, which was reduced by β,γ-methylene-ATP, an inhibitor of ectonucleotide pyrophosphorylase phosphodiesterase (NPP1).
conclusionThe ex vivo AV calcification model developed in the present study showed that extracellular PPi, produced by valvular tissue, is a potent inhibitor of valvular calcification. In addition to synthesis, hydrolysis by TNAP also controls PPi levels and calcification. The results suggest that a decreased synthesis or increased hydrolysis of pyrophosphate may contribute to valvular calcification, and that bisphosphonates or inhibitors of TNAP are potential preventive strategies of the process. TNAP are potential preventive strategies.
Indexed as
Identifiers
25803964PMC5463180W285717869What OpenQuestion holds
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.