ArticleJournal of molecular medicine (Berlin, Germany)2016
Acetazolamide sensitive tissue calcification and aging of klotho-hypomorphic mice.
Article in Journal of molecular medicine (Berlin, Germany), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 citations in OpenAlex.
- Pooled it
- Repurposing effect of cardiovascular-metabolic drug to increase lifespan: a systematic review of animal studies and current clinical trial progress.Frontiers in pharmacology · 2024Pooled it
- Phenotypic and Genotypic Characterization and Treatment of a Cohort With Familial Tumoral Calcinosis/Hyperostosis-Hyperphosphatemia Syndrome.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2016Trial
- Soft tissue accumulations of phosphate are not always associated with serum phosphate or with calcifications in mouse models of hyperphosphatemia.The Journal of physiology · 2025Article
- Soft tissue calcifications in chronic kidney disease-beyond the vasculature.Pflugers Archiv : European journal of physiology · 2025Review
- Calcification of the elastic component: the impact on the cardiovascular system.Frontiers in cardiovascular medicine · 2025Review
- Key regulators of vascular calcification in chronic kidney disease: Hyperphosphatemia, BMP2, and RUNX2.PeerJ · 2024Review
- Venous Thrombosis in a Pseudohypoparathyroidism Patient with a Novel GNAS Frameshift Mutation and Complete Resolution of Vascular Calcifications with Acetazolamide Treatment.Hormone research in paediatrics · 2024Article
- Canakinumab in addition to phosphate-binding and phosphaturia-inducing therapy were effective in achieving remission in a child with a large familial calcinotic tumour.Bone reports · 2023Article
- Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Inflammation: a putative link between phosphate metabolism and cardiovascular disease.Clinical science (London, England : 1979) · 2021Review
- The Thermodynamics of Medial Vascular Calcification.Frontiers in cell and developmental biology · 2021Review
- The Pharmacological Effect and Mechanism of Lanthanum Hydroxide on Vascular Calcification Caused by Chronic Renal Failure Hyperphosphatemia.Frontiers in cell and developmental biology · 2021Article
- Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia.Cellular and molecular life sciences : CMLS · 2019Review
- Complete heart block in a boy with hyperostosis-hyperphosphataemia syndrome: a case report.European heart journal. Case reports · 2019Article
- Therapeutic Interference With Vascular Calcification-Lessons From Klotho-Hypomorphic Mice and Beyond.Frontiers in endocrinology · 2018Review
- Impact of Altered Mineral Metabolism on Pathological Cardiac Remodeling in Elevated Fibroblast Growth Factor 23.Frontiers in endocrinology · 2018Article
- Inherited Arterial Calcification Syndromes: Etiologies and Treatment Concepts.Current osteoporosis reports · 2017Review
- Elimination of huntingtin in the adult mouse leads to progressive behavioral deficits, bilateral thalamic calcification, and altered brain iron homeostasis.PLoS genetics · 2017Article
- Novel functions of circulating Klotho.Bone · 2017Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledKlotho, a protein expressed mainly in the kidney, is required for the inhibitory effect of FGF23 on renal 1,25(OH)2D3 formation. Klotho counteracts vascular calcification and diverse age-related disorders. Klotho-hypomorphic mice (kl/kl) suffer from severe vascular calcification and rapid aging. The calcification is at least in part caused by excessive 1,25(OH)2D3, Ca(2+), and phosphate concentrations in blood, which trigger osteogenic signaling including upregulation of alkaline phosphatase (Alpl). As precipitation of calcium and phosphate is fostered by alkaline pH, extracellular acidosis could counteract tissue calcification. In order to induce acidosis, acetazolamide was added to drinking water (0.8 g/l) of kl/kl and wild-type mice. As a result, acetazolamide treatment of kl/kl mice partially reversed the growth deficit, tripled the life span, almost completely reversed the calcifications in trachea, lung, kidney, stomach, intestine, and vascular tissues, the excessive aortic alkaline phosphatase mRNA levels and the plasma concentrations of osteoprotegerin, osteopontin as well as fetuin-A, without significantly decreasing FGF23, 1,25(OH)2D3, Ca(2+), and phosphate plasma concentrations. In primary human aortic smooth muscle cells, acidotic environment prevented phosphate-induced alkaline phosphatase mRNA expression. The present study reveals a completely novel effect of acetazolamide, i.e., interference with osteoinductive signaling and tissue calcification in kl/kl mice. KEY MESSAGES: Klotho deficient (kl/kl) mice suffer from hyperphosphatemia with dramatic tissue calcification. Acetazolamide (ACM) treatment partially reversed the growth deficit of kl/kl mice. In kl/kl mice, ACM reversed tissue calcification despite continued hyperphosphatemia. ACM tripled the life span of kl/kl mice. In human aortic smooth muscle cells, low extracellular pH prevented osteogenic signaling.
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Registered trials
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