ArticleKidney international2014
Vascular calcification is dependent on plasma levels of pyrophosphate.
Article in Kidney international, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 1 of them a synthesis that pooled it.
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Who cites it
90 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.
- Urolithiasis, Independent of Uric Acid, Increased Risk of Coronary Artery and Carotid Atherosclerosis: A Meta-Analysis of Observational Studies.BioMed research international · 2020Pooled it
- Review
- Circulating Levels of Inorganic Pyrophosphate Influence the Risk and Clinical Outcomes in Calciphylaxis.JACC. Advances · 2026Article
- Chronic kidney disease: from mineral dysregulation to bone and cardiovascular disease.Journal of endocrinological investigation · 2026Review
- Calciphylaxis in children: a case series and systematic review.Pediatric nephrology (Berlin, Germany) · 2026Review
- Research trends and emerging themes in abdominal aortic calcification: a 2005-2025 bibliometric analysis.Journal of cardiothoracic surgery · 2026Review
- Considerations in the Use of Mouse Models of Vascular and Valvular Calcification.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Peripheral Vascular Calcification.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Genetic background of infantile hypophosphatemia: a narrative review.Translational pediatrics · 2026Review
- Decoding vascular calcification: mechanistic insights and translational strategies.Cellular and molecular life sciences : CMLS · 2026Review
- 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
- Inverse correlation between plasma pyrophosphate hydrolysis and early growth of abdominal aortic aneurysm: a pilot study.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Novel treatment for PXE: Recombinant ENPP1 enzyme therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Inherited phosphate and pyrophosphate disorders: New insights and novel therapies changing the oral health landscape.Journal of the American Dental Association (1939) · 2024Review
- Article
- Review
- The Purinergic Nature of Pseudoxanthoma Elasticum.Biology · 2024Review
- Humoral and cellular factors inhibit phosphate-induced vascular calcification during the growth period.Journal of clinical biochemistry and nutrition · 2023Article
- ENPP1 Immunobiology as a Therapeutic Target.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Review
- Role of the extracellular ATP/pyrophosphate metabolism cycle in vascular calcification.Purinergic signalling · 2023Review
30 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Plasma levels of pyrophosphate, an endogenous inhibitor of vascular calcification, are reduced in end-stage renal disease and correlate inversely with arterial calcification. However, it is not known whether the low plasma levels are directly pathogenic or are merely a marker of reduced tissue levels. This was tested in an animal model in which aortas were transplanted between normal mice and Enpp1(-/-) mice lacking ectonucleotide pyrophosphatase phosphodiesterase, the enzyme that synthesizes extracellular pyrophosphate. Enpp1(-/-) mice had very low plasma pyrophosphate and developed aortic calcification by 2 months that was greatly accelerated with a high-phosphate diet. Aortas of Enpp1(-/-) mice showed no further calcification after transplantation into wild-type mice fed a high-phosphate diet. Aorta allografts of wild-type mice calcified in Enpp1(-/-) mice but less so than the adjacent recipient Enpp1(-/-) aorta. Donor and recipient aortic calcium contents did not differ in transplants between wild-type and Enpp1(-/-) mice, demonstrating that transplantation per se did not affect calcification. Histology revealed medial calcification with no signs of rejection. Thus, normal levels of extracellular pyrophosphate are sufficient to prevent vascular calcification, and systemic Enpp1 deficiency is sufficient to produce vascular calcification despite normal vascular extracellular pyrophosphate production. This establishes an important role for circulating extracellular pyrophosphate in preventing vascular calcification.
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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.