Vascular Pathology of Medial Arterial Calcifications in NT5E Deficiency: Implications for the Role of Adenosine in Pseudoxanthoma Elasticum

Overview

Journal Mol Genet Metab

Specialty Endocrinology

Date 2011 Mar 5

PMID 21371928

Citations 71

Authors

Thomas C Markello

Laura K Pak

Cynthia St Hilaire

Heidi Dorward

Shira G Ziegler

Marcus Y Chen

Krishna Chaganti

Robert L Nussbaum

Manfred Boehm

William A Gahl

Affiliations

Soon will be listed here.

Abstract

Arterial Calcification due to Deficiency of CD73 (ACDC) results from mutations in the NT5E gene encoding the 5' exonucleotidase, CD73. We now describe the third familial case of ACDC, including radiological and histopathological details of the arterial calcifications. The medial lesions involve the entire circumference of the elastic lamina, in contrast to the intimal plaque-like disease of atherosclerosis. The demonstration of broken and fragmented elastic fibers leading to generalized vascular calcification suggests an analogy to pseudoxanthoma elasticum (PXE), which exhibits similar histopathology. Classical PXE is caused by deficiency of ABCC6, a C type ABC transporter whose ligand is unknown. Other C type ABC proteins transport nucleotides, so the newly described role of adenosine in inhibiting vascular calcification, along with the similarity of ACDC and PXE with respect to vascular pathology, suggests that adenosine may be the ligand for ABCC6.

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References

Jiang Q, Endo M, Dibra F, Wang K, Uitto J . Pseudoxanthoma elasticum is a metabolic disease. J Invest Dermatol. 2008; 129(2):348-54. PMC: 3169309. DOI: 10.1038/jid.2008.212. View

St Hilaire C, Ziegler S, Markello T, Brusco A, Groden C, Gill F . NT5E mutations and arterial calcifications. N Engl J Med. 2011; 364(5):432-42. PMC: 3049958. DOI: 10.1056/NEJMoa0912923. View

Doherty T, Fitzpatrick L, Inoue D, Qiao J, Fishbein M, Detrano R . Molecular, endocrine, and genetic mechanisms of arterial calcification. Endocr Rev. 2004; 25(4):629-72. DOI: 10.1210/er.2003-0015. View

Yang D, Zhang Y, Nguyen H, Koupenova M, Chauhan A, Makitalo M . The A2B adenosine receptor protects against inflammation and excessive vascular adhesion. J Clin Invest. 2006; 116(7):1913-23. PMC: 1483170. DOI: 10.1172/JCI27933. View

Yegutkin G . Nucleotide- and nucleoside-converting ectoenzymes: Important modulators of purinergic signalling cascade. Biochim Biophys Acta. 2008; 1783(5):673-94. DOI: 10.1016/j.bbamcr.2008.01.024. View

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

Moe S, ONeill K, Duan D, Ahmed S, Chen N, Leapman S . Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins. Kidney Int. 2002; 61(2):638-47. DOI: 10.1046/j.1523-1755.2002.00170.x. View

Dietz H . TGF-beta in the pathogenesis and prevention of disease: a matter of aneurysmic proportions. J Clin Invest. 2010; 120(2):403-7. PMC: 2810090. DOI: 10.1172/JCI42014. View

Miki K, Yuri T, Takeda N, Takehana K, Iwasaka T, Tsubura A . An autopsy case of pseudoxanthoma elasticum: histochemical characteristics. Med Mol Morphol. 2007; 40(3):172-7. DOI: 10.1007/s00795-007-0368-5. View

10.

Sharp J . Heredo-familial vascular and articular calcification. Ann Rheum Dis. 1954; 13(1):15-27. PMC: 1030367. DOI: 10.1136/ard.13.1.15. View

11.

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

12.

Hessle L, Johnson K, Anderson H, Narisawa S, Sali A, Goding J . Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization. Proc Natl Acad Sci U S A. 2002; 99(14):9445-9. PMC: 123160. DOI: 10.1073/pnas.142063399. View

13.

Amann K . Media calcification and intima calcification are distinct entities in chronic kidney disease. Clin J Am Soc Nephrol. 2008; 3(6):1599-605. DOI: 10.2215/CJN.02120508. View

14.

Truter S, SAPADIN A, Lebwohl M . Calcification of elastic fibers in pseudoxanthoma elasticum. Mt Sinai J Med. 1996; 63(3-4):210-5. View

15.

Le Boulanger G, Labreze C, Croue A, Schurgers L, Chassaing N, Wittkampf T . An unusual severe vascular case of pseudoxanthoma elasticum presenting as generalized arterial calcification of infancy. Am J Med Genet A. 2009; 152A(1):118-23. DOI: 10.1002/ajmg.a.33162. View

16.

Sager G, Ravna A . Cellular efflux of cAMP and cGMP - a question about selectivity. Mini Rev Med Chem. 2009; 9(8):1009-13. DOI: 10.2174/138955709788681654. View

17.

Zhou S, Wang L, Di Y, Xue C, Duan W, Li C . Substrates and inhibitors of human multidrug resistance associated proteins and the implications in drug development. Curr Med Chem. 2008; 15(20):1981-2039. DOI: 10.2174/092986708785132870. View

18.

Normand J, KARASEK M . A method for the isolation and serial propagation of keratinocytes, endothelial cells, and fibroblasts from a single punch biopsy of human skin. In Vitro Cell Dev Biol Anim. 1995; 31(6):447-55. DOI: 10.1007/BF02634257. View

19.

Deeley R, Westlake C, Cole S . Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins. Physiol Rev. 2006; 86(3):849-99. DOI: 10.1152/physrev.00035.2005. View