Mechanistic Insights into Vascular Calcification in CKD : Journal of the American Society of Nephrology (original) (raw)
Up Front Matters
*Nephro-Urology Unit, Great Ormond Street Hospital for Children and University College London Institute of Child Health, London, United Kingdom; and
†BHF Centre, Division of Cardiovascular Medicine, Kings College London, London, United Kingdom
Correspondence: Dr. Rukshana Shroff, Nephro-Urology Unit, Great Ormond Street Hospital for Children and University College London Institute of Child Health, London WC1N 3JH, UK. Email: [email protected]
Abstract
Cardiovascular disease begins early in the course of renal decline and is a life-limiting problem in patients with CKD. The increased burden of cardiovascular disease is due, at least in part, to calcification of the vessel wall. The uremic milieu provides a perfect storm of risk factors for accelerated calcification, but elevated calcium and phosphate levels remain key to the initiation and progression of vascular smooth muscle cell calcification in CKD. Vascular calcification is a highly regulated process that involves a complex interplay between promoters and inhibitors of calcification and has many similarities to bone ossification. Here, we discuss current understanding of the process of vascular calcification, focusing specifically on the discrete and synergistic effects of calcium and phosphate in mediating vascular smooth muscle cell apoptosis, osteochondrocytic differentiation, vesicle release, calcification inhibitor expression, senescence, and death. Using our model of intact human vessels, factors initiating vascular calcification in vivo and the role of calcium and phosphate in driving accelerated calcification ex vivo are described. This work allows us to link clinical and basic research into a working theoretical model to explain the pathway of development of vascular calcification in CKD.
Copyright © 2013 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
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