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Dietary Pyrophosphate Modulates Calcification in a Mouse Model of Pseudoxanthoma Elasticum: Implication for Treatment of Patients

Abstract :

Pseudoxanthoma elasticum (PXE) is a heritable disease caused by ABCC6 deficiency. Patients develop ectopic calcification in skin, eyes and vascular tissues. ABCC6, primarily found in liver and kidneys, mediates the cellular efflux of ATP, which is rapidly converted into pyrophosphate (PPi), a potent inhibitor of calcification. PXE patients and Abcc6 mice display reduced PPi levels in plasma and peripheral tissues. PXE is currently incurable, although some palliative treatments exist. In recent years, we have successfully developed therapeutic methodologies to compensate the PPi deficit in animal models and humans. Here, we inadvertently discovered that modulating dietary PPi can also be an effective approach to reducing calcification in Abcc6 mice. Our findings were prompted by a change in institutional rodent diet. The new chow was enriched in PPi, which increased plasma PPi, and significantly reduced mineralization in Abcc6 mice. We also found that dietary PPi is readily absorbed in humans. Our results suggest that the consumption of food naturally or artificially enriched in PPi represents a possible intervention to mitigate calcification progression in PXE, that dietary preferences of patients may explain PXE heterogeneous manifestations and that animal chow has the potential to influence data reproducibility.

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https://hal.univ-angers.fr/hal-02616918
Contributeur : Okina Université d'Angers <>
Soumis le : lundi 25 mai 2020 - 04:40:47
Dernière modification le : mardi 26 mai 2020 - 03:48:28

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Viola Pomozi, Charnelle Julian, Janna Zoll, Kevin Pham, Sheree Kuo, et al.. Dietary Pyrophosphate Modulates Calcification in a Mouse Model of Pseudoxanthoma Elasticum: Implication for Treatment of Patients. The journal of investigative dermatology, 2019, 139 (5), pp.1082-1088. ⟨10.1016/j.jid.2018.10.040⟩. ⟨hal-02616918⟩

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