Premium
Molecular mechanisms mediating vascular calcification: Role of matrix Gla protein (Review Article)
Author(s) -
PROUDFOOT DIANE,
SHANAHAN CATHERINE M
Publication year - 2006
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/j.1440-1797.2006.00660.x
Subject(s) - matrix gla protein , calcification , extracellular matrix , vascular smooth muscle , calcium , medicine , vitamin d and neurology , microbiology and biotechnology , bone morphogenetic protein 2 , endocrinology , bone morphogenetic protein , ectopic calcification , biochemistry , biology , smooth muscle , in vitro , gene
SUMMARY: Patients with chronic kidney disease (CKD) have a higher incidence of vascular calcification and a greatly increased risk of cardiovascular death. The mechanisms involved in the accelerated vascular calcification observed in CKD have recently become clearer, leading to the hypothesis that a lack of natural inhibitors of calcification may trigger calcium deposition. One of these inhibitory factors, matrix Gla protein (MGP), is the focus of the present review. MGP, originally isolated from bone, is a vitamin K‐dependent protein that is also highly expressed by vascular smooth muscle cells. MGP has been confirmed as a calcification‐inhibitor in numerous studies; however, its mechanism of action is not completely understood. It potentially acts in several ways to regulate calcium deposition including: (i) binding calcium ions and crystals; (ii) antagonizing bone morphogenetic protein and altering cell differentiation; (iii) binding to extracellular matrix components; and (iv) regulating apoptosis. Its expression is regulated by several factors including retinoic acid, vitamin D and extracellular calcium ions, and a reduced form of vitamin K (KH 2 ) is important in maintaining MGP in an active form. Therefore, strategies aimed at increasing its expression and activity may be beneficial in tipping the balance in favour of inhibition of calcification in CKD.