Vascular Calcification Revisited: A New Perspective for Phosphate Transport

Overview

Journal Curr Cardiol Rev

Publisher Bentham Science Publishers

Specialty Cardiology & Vascular Diseases

Date 2015 Aug 6

PMID 26242187

Citations 8

Authors

Ricardo Villa-Bellosta

Affiliations

Soon will be listed here.

Abstract

Elevated serum phosphorus has emerged as a key risk factor for pathologic calcification of cardiovascular structures, or vascular calcification (VC). To prevent the formation of calciumphosphate deposits (CPD), the body uses adenosine-5’-triphosphate (ATP) to synthesize inhibitors of calcification, including proteins and inhibitors of low molecular weight. Extracellular pyrophosphate (PPi) is a potent inhibitor of VC, which is produced during extracellular hydrolysis of ATP. Loss of function in the enzymes and transporters that are involved in the cycle of extracellular ATP, including Pi transporters, leads to excessive deposition of calcium-phosphate salts. Treatment of hyperphosphatemia with Pi-binders and Injection of exogenous PPi are the effective treatments to prevent CPD in the aortic wall. The role of sodium phosphate cotransporters in ectopic calcification is contradictory and not well defined, but their important role in the control of intracellular Pi levels and the synthesis of ATP make them an important target to study.

Citing Articles

Vascular Calcification: Key Roles of Phosphate and Pyrophosphate.

Villa-Bellosta R Int J Mol Sci. 2021; 22(24).

PMID: 34948333 PMC: 8708352. DOI: 10.3390/ijms222413536.

Hydrolysis of Extracellular Pyrophosphate increases in post-hemodialysis plasma.

Azpiazu D, Gonzalez-Parra E, Egido J, Villa-Bellosta R Sci Rep. 2018; 8(1):11089.

PMID: 30038263 PMC: 6056505. DOI: 10.1038/s41598-018-29432-4.

Etidronate prevents dystrophic cardiac calcification by inhibiting macrophage aggregation.

Bauer C, Le Saux O, Pomozi V, Aherrahrou R, Kriesen R, Stolting S Sci Rep. 2018; 8(1):5812.

PMID: 29643466 PMC: 5895639. DOI: 10.1038/s41598-018-24228-y.

Impact of post-dialysis calcium level on ex vivo rat aortic wall calcification.

Azpiazu D, Gonzalez-Parra E, Ortiz A, Egido J, Villa-Bellosta R PLoS One. 2017; 12(8):e0183730.

PMID: 28832652 PMC: 5568142. DOI: 10.1371/journal.pone.0183730.

[Effect of HBP-A on meniscal injury and pathological hypertrophy and calcification of the meniscus].

Du G, Ding D, Feng Y, Li L, Lei T, Chen B Nan Fang Yi Ke Da Xue Xue Bao. 2017; 37(4):431-437.

PMID: 28446392 PMC: 6744102.

References

Le Saux O, Urban Z, Tschuch C, Csiszar K, Bacchelli B, Quaglino D . Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Nat Genet. 2000; 25(2):223-7. DOI: 10.1038/76102. View

Bergen A, Plomp A, Schuurman E, Terry S, Breuning M, Dauwerse H . Mutations in ABCC6 cause pseudoxanthoma elasticum. Nat Genet. 2000; 25(2):228-31. DOI: 10.1038/76109. View

Ho A, Johnson M, Kingsley D . Role of the mouse ank gene in control of tissue calcification and arthritis. Science. 2000; 289(5477):265-70. DOI: 10.1126/science.289.5477.265. View

Schinke T, Karsenty G . Vascular calcification--a passive process in need of inhibitors. Nephrol Dial Transplant. 2000; 15(9):1272-4. DOI: 10.1093/ndt/15.9.1272. View

Jono S, McKee M, Murry C, Shioi A, Nishizawa Y, Mori K . Phosphate regulation of vascular smooth muscle cell calcification. Circ Res. 2000; 87(7):E10-7. DOI: 10.1161/01.res.87.7.e10. View

Proudfoot D, Skepper J, Hegyi L, Bennett M, Shanahan C, Weissberg P . Apoptosis regulates human vascular calcification in vitro: evidence for initiation of vascular calcification by apoptotic bodies. Circ Res. 2000; 87(11):1055-62. DOI: 10.1161/01.res.87.11.1055. View

Zimmermann H . Extracellular metabolism of ATP and other nucleotides. Naunyn Schmiedebergs Arch Pharmacol. 2000; 362(4-5):299-309. DOI: 10.1007/s002100000309. View

Mansfield K, Teixeira C, Adams C, Shapiro I . Phosphate ions mediate chondrocyte apoptosis through a plasma membrane transporter mechanism. Bone. 2001; 28(1):1-8. DOI: 10.1016/s8756-3282(00)00409-9. View

Nurnberg P, Thiele H, Chandler D, Hohne W, Cunningham M, Ritter H . Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia. Nat Genet. 2001; 28(1):37-41. DOI: 10.1038/ng0501-37. View

10.

Reichenberger E, Tiziani V, Watanabe S, Park L, Ueki Y, SantAnna C . Autosomal dominant craniometaphyseal dysplasia is caused by mutations in the transmembrane protein ANK. Am J Hum Genet. 2001; 68(6):1321-6. PMC: 1226118. DOI: 10.1086/320612. View

11.

LeGeros R . Formation and transformation of calcium phosphates: relevance to vascular calcification. Z Kardiol. 2001; 90 Suppl 3:116-24. DOI: 10.1007/s003920170032. View

12.

Kanzaki N, Treboux G, Onuma K, Tsutsumi S, Ito A . Calcium phosphate clusters. Biomaterials. 2001; 22(21):2921-9. DOI: 10.1016/s0142-9612(01)00039-4. View

13.

Steitz S, Speer M, Curinga G, Yang H, Haynes P, Aebersold R . Smooth muscle cell phenotypic transition associated with calcification: upregulation of Cbfa1 and downregulation of smooth muscle lineage markers. Circ Res. 2001; 89(12):1147-54. DOI: 10.1161/hh2401.101070. View

14.

Stout C, Costantin J, Naus C, Charles A . Intercellular calcium signaling in astrocytes via ATP release through connexin hemichannels. J Biol Chem. 2002; 277(12):10482-8. DOI: 10.1074/jbc.M109902200. View

15.

Koshizuka Y, Ikegawa S, Sano M, Nakamura K, Nakamura Y . Isolation of novel mouse genes associated with ectopic ossification by differential display method using ttw, a mouse model for ectopic ossification. Cytogenet Cell Genet. 2002; 94(3-4):163-8. DOI: 10.1159/000048809. View

16.

Segawa H, Kaneko I, Takahashi A, Kuwahata M, Ito M, Ohkido I . Growth-related renal type II Na/Pi cotransporter. J Biol Chem. 2002; 277(22):19665-72. DOI: 10.1074/jbc.M200943200. View

17.

Pendleton A, Johnson M, Hughes A, Gurley K, Ho A, Doherty M . Mutations in ANKH cause chondrocalcinosis. Am J Hum Genet. 2002; 71(4):933-40. PMC: 378546. DOI: 10.1086/343054. View

18.

Williams C, Zhang Y, Timms A, Bonavita G, Caeiro F, Broxholme J . Autosomal dominant familial calcium pyrophosphate dihydrate deposition disease is caused by mutation in the transmembrane protein ANKH. Am J Hum Genet. 2002; 71(4):985-91. PMC: 419998. DOI: 10.1086/343053. View

19.

Collins J, Bai L, Ghishan F . The SLC20 family of proteins: dual functions as sodium-phosphate cotransporters and viral receptors. Pflugers Arch. 2003; 447(5):647-52. DOI: 10.1007/s00424-003-1088-x. View

20.

Rutsch F, Ruf N, Vaingankar S, Toliat M, Suk A, Hohne W . Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification. Nat Genet. 2003; 34(4):379-81. DOI: 10.1038/ng1221. View