Ectopic calcification: importance of common nanoparticle scaffolds containing oxidized acidic lipids

This article presents a scoping review and synthesis of research findings investigating the toxic cellular accumulation of dysregulated inorganic phosphate—phosphate toxicity—as a pathophysiological determinant of diabetes and diabetic complications. Phosphorus, an essential micronutrient, is closely linked to the cellular metabolism of glucose for energy production, and serum inorganic phosphate is often transported into cells along with glucose during insulin therapy. Mitochondrial dysfunction and apoptosis, endoplasmic reticulum stress, neuronal degeneration, and pancreatic cancer are associated with dysregulated levels of phosphate in diabetes. Ectopic calcification involving deposition of calcium-phosphate crystals is prevalent throughout diabetic complications, including vascular calcification, nephropathy, retinopathy, and bone disorders. A low-glycemic, low-phosphate dietary intervention is proposed for further investigations in the treatment and prevention of diabetes and related diabetic pathologies.

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Effect of sodium fluoride on the lead-induced ectopic calcification

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)48522-3 ◽

2000 ◽

Vol 82 ◽

pp. 265

Author(s):

Shigeki Mizutani ◽

Michitsugu Arai ◽

Akifumi Togari

Keyword(s):

Sodium Fluoride ◽

Ectopic Calcification

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Gitelman syndrome and ectopic calcification in the retina and joints

Clinical Kidney Journal ◽

10.1093/ckj/sfab034 ◽

2021 ◽

Author(s):

Yeji Ham ◽

Heather Mack ◽

Deb Colville ◽

Philip Harraka ◽

B Biomed ◽

...

Keyword(s):

Calcium Pyrophosphate ◽

Bartter Syndrome ◽

Gitelman Syndrome ◽

Ectopic Calcification ◽

Aggressive Management ◽

Renal Tubular Disorder ◽

Rate Of Progression ◽

Renal Tubular ◽

Retinal Photography

ABSTRACT Gitelman syndrome is a rare inherited renal tubular disorder with features that resemble thiazide use, including a hypokalemic metabolic alkalosis, hypomagnesemia, hypocalciuria, a low or normal blood pressure, and hyperreninemia and hyperaldosteronism. Treatment is primarily correction of the K and Mg levels. The diagnosis is confirmed with genetic testing but Gitelman syndrome is often not suspected. However the association with ectopic calcification in the retina, blood vessels and chondrocalcinosis in the joints is a useful pointer to this diagnosis. Bilateral symmetrical whitish deposits of calcium pyrophosphate are visible superotemporally on ophthalmoscopy and retinal photography but are actually located beneath the retina in the sclerochoroid. Optical coherence tomography is even more sensitive for their detection. These deposits increase in size with time, but the rate of progression slows with long-term correction of the hypomagnesemia. Calcification may be complicated by atrophy of the overlying retina and visual loss. The deposits often correlate with ectopic calcification in the aorta, coronary and cerebral vessels. Chondrocalcinosis occurs in the large joints such as the knees. Ectopic calcification in Gitelman syndrome indicates the need for more aggressive management of Ca and Mg levels. Calcification is much less common in Bartter syndrome which itself is rarer and associated less often with hypomagnesemia.

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Disruption of Abcc6 Transporter in Zebrafish Causes Ocular Calcification and Cardiac Fibrosis

International Journal of Molecular Sciences ◽

10.3390/ijms22010278 ◽

2020 ◽

Vol 22 (1) ◽

pp. 278

Author(s):

Jianjian Sun ◽

Peilu She ◽

Xu Liu ◽

Bangjun Gao ◽

Daqin Jin ◽

...

Keyword(s):

Vitamin K ◽

Cardiac Fibrosis ◽

Clinical Manifestations ◽

Pseudoxanthoma Elasticum ◽

Matrix Gla Protein ◽

Ectopic Calcification ◽

Transcription Activator ◽

Multisystem Disorder ◽

Ectopic Mineralization ◽

Extensive Calcification

Pseudoxanthoma elasticum (PXE), caused by ABCC6/MRP6 mutation, is a heritable multisystem disorder in humans. The progressive clinical manifestations of PXE are accompanied by ectopic mineralization in various connective tissues. However, the pathomechanisms underlying the PXE multisystem disorder remains obscure, and effective treatment is currently available. In this study, we generated zebrafish abcc6a mutants using the transcription activator-like effector nuclease (TALEN) technique. In young adult zebrafish, abcc6a is expressed in the eyes, heart, intestine, and other tissues. abcc6a mutants exhibit extensive calcification in the ocular sclera and Bruch’s membrane, recapitulating part of the PXE manifestations. Mutations in abcc6a upregulate extracellular matrix (ECM) genes, leading to fibrotic heart with reduced cardiomyocyte number. We found that abcc6a mutation reduced levels of both vitamin K and pyrophosphate (PPi) in the serum and diverse tissues. Vitamin K administration increased the gamma-glutamyl carboxylated form of matrix gla protein (cMGP), alleviating ectopic calcification and fibrosis in vertebrae, eyes, and hearts. Our findings contribute to a comprehensive understanding of PXE pathophysiology from zebrafish models.

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Massive ectopic calcification of the leg following nerve injury

Archives of Orthopaedic and Traumatic Surgery ◽

10.1007/bf02498720 ◽

1983 ◽

Vol 102 (2) ◽

pp. 82-87 ◽

Cited By ~ 5

Author(s):

K. Österman ◽

T. Sam Lindholm

Keyword(s):

Nerve Injury ◽

Ectopic Calcification

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Ectopic calcification in β-thalassemia patients is associated with increased oxidative stress and lower MGP carboxylation

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease ◽

10.1016/j.bbadis.2013.07.017 ◽

2013 ◽

Vol 1832 (12) ◽

pp. 2077-2084 ◽

Cited By ~ 13

Author(s):

Federica Boraldi ◽

Maria Garcia-Fernandez ◽

Chiara Paolinelli-deVincenzi ◽

Giulia Annovi ◽

Leon Schurgers ◽

...

Keyword(s):

Oxidative Stress ◽

Ectopic Calcification

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Alteration of acidic lipids in human sera during the course of pregnancy: characteristic increase in the concentration of cholesterol sulfate

Journal of Chromatography B Biomedical Sciences and Applications ◽

10.1016/s0378-4347(97)00450-7 ◽

1997 ◽

Vol 704 (1-2) ◽

pp. 99-104 ◽

Cited By ~ 13

Author(s):

Bei Lin ◽

Kaneyuki Kubushiro ◽

Yasuo Akiba ◽

Yongxi Cui ◽

Katsumi Tsukazaki ◽

...

Keyword(s):

Cholesterol Sulfate ◽

Human Sera ◽

Acidic Lipids

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Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b+/− mice

AJP Renal Physiology ◽

10.1152/ajprenal.00663.2010 ◽

2011 ◽

Vol 301 (5) ◽

pp. F1105-F1113 ◽

Cited By ~ 31

Author(s):

Akiko Ohi ◽

Etsuyo Hanabusa ◽

Otoya Ueda ◽

Hiroko Segawa ◽

Naoshi Horiba ◽

...

Keyword(s):

Inorganic Phosphate ◽

Fibroblast Growth Factor 23 ◽

High Plasma ◽

Phosphate Binders ◽

Ectopic Calcification ◽

Activity Levels ◽

Mrna Levels ◽

Distal Intestine ◽

Transporter Protein ◽

Sodium Dependent

An inorganic phosphate (Pi)-restricted diet is important for patients with chronic kidney disease and patients on hemodialysis. Phosphate binders are essential for preventing hyperphosphatemia and ectopic calcification. The sodium-dependent Pi (Na/Pi) transport system is involved in intestinal Pi absorption and is regulated by several factors. The type II sodium-dependent Pi transporter Npt2b is expressed in the brush-border membrane in intestinal epithelial cells and transports Pi. In the present study, we analyzed the phenotype of Npt2b−/− and hetero+/− mice. Npt2b−/− mice died in utero soon after implantation, indicating that Npt2b is essential for early embryonic development. At 4 wk of age, Npt2b+/− mice showed hypophosphatemia and low urinary Pi excretion. Plasma fibroblast growth factor 23 levels were significantly decreased and 1,25(OH)2D3 levels were significantly increased in Npt2b+/− mice compared with Npt2b+/+ mice. Npt2b mRNA levels were reduced to 50% that in Npt2b+/+ mice. In contrast, renal Npt2a and Npt2c transporter protein levels were significantly increased in Npt2b+/− mice. At 20 wk of age, Npt2b+/− mice showed hypophosphaturia and reduced Na/Pi cotransport activity in the distal intestine. Npt2b+/+ mice with adenine-induced renal failure had hyperphosphatemia and high plasma creatinine levels. Npt2b+/− mice treated with adenine had significantly reduced plasma Pi levels compared with Npt2b+/+ mice. Intestinal Npt2b protein and Na+/Pi transport activity levels were significantly lower in Npt2b+/− mice than in the Npt2b+/+ mice. The findings of the present studies suggest that Npt2b is an important target for the prevention of hyperphosphatemia.

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