A Vascular Bone Collector

Abstract

See related article, pages 529–537 Calcification of the arterial wall occurs in, among others, atherosclerosis and aging. The role of calcification in plaque stability is subject of ongoing discussion; media calcification in aging and diabetes increases stiffness and pulse pressure.1 It is now clear that calcification is not simply a passive process but, rather, is tightly regulated, involving induction of an osteochondrogenic phenotype in the vascular smooth muscle cells (VSMCs) and control of expression and activity of factors promoting and inhibiting calcium deposition. In this issue of Circulation Research , Johnson et al2 provide evidence that transglutaminases (Tgases), cross-linking enzymes with recently discovered vascular functions, are required for inducing the vascular calcification process. Tgases are multifunctional enzymes acting in the cell, at the cell surface, or as released enzymes. Their most prominent feature is the covalent cross-linking of proteins.3 The glutamine–lysine cross-links, either within or between proteins, result in the stabilization of extracellular matrices and the binding of signaling molecules, such as osteopontin, to the matrix but also the prolonged activation of angiotensin II receptors through dimerization.4 Cell surface Tgases are involved in cell adhesion through integrin clustering and function as coreceptors in the binding to fibronectin.5 The Tgase family consists of 9 members, of which TG1, TG2, and the coagulation factor XIIIA are expressed in the arterial wall.6 The tissue-type Tgase studied here (TG2) fulfills both cross-linking activities and G protein …