Uremic vascular calcification.
Recent evidence suggests that uremic vascular calcification is an active, cell-mediated process resembling osteogenesis in bone rather than passive precipitation. We identified increased expression of bone-associated proteins (osteopontin, bone sialoprotein, alkaline phosphatase, type I collagen) and the bone-specific transcription factor core-binding factor alpha(1) (Cbfalpha(1)) in histologic sections of inferior epigastric arteries obtained from patients with stage V chronic kidney disease or calcific uremic arteriolopathy. In in vitro experiments, the addition of uremic serum to cultured vascular smooth muscle cells up-regulated osteopontin and Cbfalpha(1) expression and accelerated mineralization. This implies that the uremic mileau may lead to dedifferentiation of vascular smooth muscle cells, with subsequent mineralization. However, a lack of inhibitors of calcification may also be important. Dialysis patients with low levels of serum fetuin A, a circulating inhibitor of mineralization, have increased coronary artery calcification, and fetuin A can inhibit mineralization of vascular smooth muscle cells in vitro. Further understanding of the pathophysiology of uremic vascular calcification is needed to design effective therapeutic strategies to intervene with this devastating condition in patients with stage V chronic kidney disease.
Chen
Neal X
NX
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. xuechen@inpui.edu
Moe
Sharon M
SM
D000818:Animals; D001798:Blood Proteins / Q000502:physiology; D002114:Calcinosis / Q000209:etiology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000502:physiology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D010012:Osteogenesis; D014511:Uremia / Q000150:complications*; D014652:Vascular Diseases / Q000209:etiology*; D060749:alpha-2-HS-Glycoprotein
C556354:AHSG protein, human; D001798:Blood Proteins; D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human; D060749:alpha-2-HS-Glycoprotein