ArticlePloS one2020
Lumenal calcification and microvasculopathy in fetuin-A-deficient mice lead to multiple organ morbidity.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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
28 citing papers in PubMed, 53 citations in OpenAlex.
- Effect of the phosphate binder sucroferric oxyhydroxide in dialysis patients on endogenous calciprotein particles, inflammation, and vascular cells.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Trial
- Effect of lanthanum carbonate on serum calciprotein particles in patients with stage 3-4 CKD-results from a placebo-controlled randomized trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Trial
- The effects of elevated phosphate on the kidney - damaging the gatekeeper.Pflugers Archiv : European journal of physiology · 2026Review
- Peripheral Vascular Calcification.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Soft tissue calcifications in chronic kidney disease-beyond the vasculature.Pflugers Archiv : European journal of physiology · 2025Review
- The formation and function of calciprotein particles.Pflugers Archiv : European journal of physiology · 2025Review
- [Sevelamer vs. Calcium Acetate for Treating Hyperphosphatemia in Maintenance Hemodialysis Patients].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- Role of Uremic Toxins in Vascular Inflammation Associated with Chronic Kidney Disease.Journal of clinical medicine · 2024Article
- Accelerated calciprotein crystallization time (T50) is correlated with impaired lung diffusion capacity in systemic sclerosis.Frontiers in immunology · 2024Article
- Calciprotein Particles Induce Cellular Compartment-Specific Proteome Alterations in Human Arterial Endothelial Cells.Journal of cardiovascular development and disease · 2023Article
- Inflammation and gut dysbiosis as drivers of CKD-MBD.Nature reviews. Nephrology · 2023Review
- Increased UHMWPE Particle-Induced Osteolysis in Fetuin-A-Deficient Mice.Journal of functional biomaterials · 2023Article
- Application of the mineral-binding protein fetuin-A for the detection of calcified lesions.Theranostics · 2023Article
- Novel insights into osteocyte and inter-organ/tissue crosstalk.Frontiers in endocrinology · 2023Review
- Article
- Tissue chaperoning-the expanded functions of fetuin-A beyond inhibition of systemic calcification.Pflugers Archiv : European journal of physiology · 2022Review
- INZ-701, a recombinant ENPP1 enzyme, prevents ectopic calcification in an Abcc6Experimental dermatology · 2022Article
- Level of Serum Fetuin-A Correlates with Heart Rate in Obstructive Sleep Apnea Patients without Metabolic and Cardiovascular Comorbidities.International journal of environmental research and public health · 2022Article
- Effect of nutritional calcium and phosphate loading on calciprotein particle kinetics in adults with normal and impaired kidney function.Scientific reports · 2022Article
- Serum levels of fetuin-A as a novel biomarker for disease activity in patients with Takayasu arteritis and granulomatous polyangiitis.Clinical rheumatology · 2022Article
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
The plasma protein fetuin-A mediates the formation of protein-mineral colloids known as calciprotein particles (CPP)-rapid clearance of these CPP by the reticuloendothelial system prevents errant mineral precipitation and therefore pathological mineralization (calcification). The mutant mouse strain D2,Ahsg-/- combines fetuin-A deficiency with the calcification-prone DBA/2 genetic background, having a particularly severe compound phenotype of microvascular and soft tissue calcification. Here we studied mechanisms leading to soft tissue calcification, organ damage and death in these mice. We analyzed mice longitudinally by echocardiography, X-ray-computed tomography, analytical electron microscopy, histology, mass spectrometry proteomics, and genome-wide microarray-based expression analyses of D2 wildtype and Ahsg-/- mice. Fetuin-A-deficient mice had calcified lesions in myocardium, lung, brown adipose tissue, reproductive organs, spleen, pancreas, kidney and the skin, associated with reduced growth, cardiac output and premature death. Importantly, early-stage calcified lesions presented in the lumen of the microvasculature suggesting precipitation of mineral containing complexes from the fluid phase of blood. Genome-wide expression analysis of calcified lesions and surrounding (not calcified) tissue, together with morphological observations, indicated that the calcification was not associated with osteochondrogenic cell differentiation, but rather with thrombosis and fibrosis. Collectively, these results demonstrate that soft tissue calcification can start by intravascular mineral deposition causing microvasculopathy, which impacts on growth, organ function and survival. Our study underscores the importance of fetuin-A and related systemic regulators of calcified matrix metabolism to prevent cardiovascular disease, especially in dysregulated mineral homeostasis.
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Registered trials
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