The bone-vasculature-axis interaction: new insights into the pathogenesis of vascular calcification

It is commonly accepted that the first cause of morbidity and mortality in chronic kidney disease (CKD) is the cardiovascular (CV) disease, in which vascular calcification (VC) plays a central pathogenetic role. In CKD population, mineral metabolism disorders have been recently investigated not only as key factors on renal osteodystrophy but also as inducing players on extra-skeletal calcification. Clearly, either high phosphate (P) or high calcium (Ca) concentration induce vascular smooth muscle cells mineralization in vitro studies. In fact, VC is induced by a cell-mediated process, which actively accompanies the traditional and passive Ca-P deposition in arterial walls. Interestingly, lack of inhibitory proteins, such as fetuin-A (alpha2-HS glycoprotein, AHSG), matrix GLA protein (MGP), osteoprotegerin (OPG), and bone morphogenetic protein 7 (BMP-7) are the regulatory key factors in preventing VC in uremic conditions.