A new in vitro model to delay high phosphate-induced vascular calcification progression

Molecular and Cellular Biochemistry
Paola CiceriMario Cozzolino

Abstract

An increasing amount of patients affected by advanced chronic kidney disease suffer from vascular calcification (VC) that associates with cardiovascular morbidity and mortality. In this study, we created a new experimental in vitro model, trying to better elucidate high phosphate (Pi)-induced VC pathogenic mechanisms. Rat aortic vascular smooth muscle cells (VSMCs) were challenged for 7-10 days with high Pi with a repeated and short suspensions of high Pi treatment (intermittent suspension, IS) that was able to induce a significant inhibition of high Pi calcification, maximal at 5 h. Interestingly, the delay in calcification is a consequence of either the absence of free Pi or calcium-phosphate crystals being comparable to the total effect obtained during the 5 h-IS. The protective effect of IS was mediated by the reduction of apoptosis as demonstrated by the action of 20 μmol/L Z-VAD-FMK and by the preservation of the pro-survival receptor Axl expression. Furthermore, autophagy, during IS, was potentiated by increasing the autophagic flux, evaluated by LC3IIB western, while treating VSMCs with 1 mmol/L valproic acid did not affect VC. Finally, IS prevented VSMC osteoblastic differentiation by preserving smooth muscle lineage m...Continue Reading

References

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Citations

Apr 12, 2019·Toxins·Mario CozzolinoGiuseppe Cianciolo
Nov 22, 2016·Nature Reviews. Nephrology·Marc G VervloetUNKNOWN ERA–EDTA Working Group on Chronic Kidney Disease–Mineral and Bone Disorders and the European Renal Nutrition Working Group
Nov 30, 2019·International Journal of Molecular Sciences·Paola CiceriMario Cozzolino
Dec 2, 2020·International Journal of Molecular Sciences·Cédric H G NeutelPieter-Jan Guns
Mar 30, 2021·Clinical Kidney Journal·Paola Ciceri, Mario Cozzolino
Dec 5, 2016·Kidney International·Marc Vervloet, Mario Cozzolino
Aug 18, 2021·Cell & Bioscience·Xin ZhouHui-Ling Cao

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