Vitamin K does not prevent soft tissue mineralization in a mouse model of pseudoxanthoma elasticum

Cell Cycle. 2011 Jun 1;10(11):1810-20. doi: 10.4161/cc.10.11.15681. Epub 2011 Jun 1.

Abstract

Pseudoxanthoma elasticum (PXE) is a heritable disease characterized by calcified elastic fibers in cutaneous, ocular, and vascular tissues. PXE is caused by mutations in ABCC6, which encodes a protein of the ATP-driven organic anion transporter family. The inability of this transporter to secrete its substrate into the circulation is the likely cause of PXE. Vitamin K plays a role in the regulation of mineralization processes as a co-factor in the carboxylation of calcification inhibitors such as Matrix Gla Protein (MGP). Vitamin K precursor or a conjugated form has been proposed as potential substrate(s) for ABCC6. We investigated whether an enriched diet of vitamin K1 or vitamin K2 (MK4) could stop or slow the disease progression in Abcc6 (-/-) mice. Abcc6 (-/-) mice were placed on a diet of either vitamin K1 or MK4 at 5 or 100 mg/kg at prenatal, 3 weeks or 3 months of age. Disease progression was quantified by measuring the calcium content of one side of the mouse muzzle skin and histological staining for calcium of the opposing side. Raising the vitamin K1 or MK4 content of the diet increased the concentration of circulating MK4 in the serum. However, this increase did not significantly affect the MGP carboxylation status or reduce its abnormal abundance, the total calcium content or the pathologic calcification in the whiskers of the 3 treatment groups compared to controls. Our findings showed that raising the dietary intake of vitamin K1 or MK4 was not beneficial in the treatment of PXE and suggested that the availability of vitamin K may not be a limiting factor in this pathology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Animals
  • Calcinosis*
  • Dietary Supplements
  • Disease Models, Animal
  • Mice
  • Mice, Knockout
  • Multidrug Resistance-Associated Proteins
  • Pseudoxanthoma Elasticum / drug therapy*
  • Pseudoxanthoma Elasticum / metabolism
  • Pseudoxanthoma Elasticum / pathology
  • Treatment Failure
  • Vitamin K / administration & dosage*
  • Vitamin K / physiology

Substances

  • ATP-Binding Cassette Transporters
  • Abcc6 protein, mouse
  • Multidrug Resistance-Associated Proteins
  • Vitamin K