Abstract
The causes of arterial calcification are beginning to be elucidated. Macrophages, mast cells, and smooth muscle cells are the primary cells implicated in this process. The roles of a variety of boneโrelated proteins including bone morphogenetic proteinโ2 (BMPโ2), matrix Gla protein (MGP), osteoprotegerin (OPG), osteopontin, and osteonectin in regulating arterial calcification are reviewed. Animals lacking MGP, OPG, smad6, carbonic anhydrase isoenzyme II, fibrillinโ1, and klotho gene product develop varying extents of arterial calcification. Hyperlipidemia, vitamin D, nicotine, and warfarin, alone or in various combinations, produce arterial calcification in animal models. MGP has recently been discovered to be an inhibitor of bone morphogenetic proteinโ2, the principal osteogenic growth factor. Many of the forces that induce arterial calcification may act by disrupting the essential postโtranslational modification of MGP, allowing BMPโ2 to induce mineralization. MGP requires gammaโcarboxylation before it is functional, and this process uses vitamin K as an essential cofactor. Vitamin K deficiency, drugs that act as vitamin K antagonists, and oxidant stress are forces that could prevent the formation of GLA residues on MGP. The potential role of arterial apoptosis in calcification is discussed. Potential therapeutic options to limit the rate of arterial calcification are summarized. ยฉ 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 4, 274โ301, 2001