Vascular calcification.
OBJECTIVE
Accumulating evidence suggests that the high cardiovascular mortality observed in patients with end-stage renal disease is due in part to the deleterious effects of vascular calcification that develops over time on dialysis. This review focuses on recent cell biological and animal studies that have shed light on the mechanisms and regulators of vascular smooth muscle cell calcification in end-stage renal disease.


RESULTS
Clinical studies demonstrate that high circulating levels of phosphate or calcium predict vascular calcification. Recent cell biological studies have provided novel insights into how vascular smooth muscle cells regulate calcification in response to such insults. Vascular smooth muscle cell damage and subsequent vesicle release from viable and dying cells create an environment permissive for the nucleation of basic calcium phosphate mineral. This, combined with osteogenic conversion of vascular smooth muscle cells and consequent loss of their normal inhibitory processes/pathways, results in calcification. Circulating factors such as fetuin-A, with the potential to impact on vessel wall calcification, have also been identified. Animal studies suggest that the 'uremic milieu' potentiates calcification and have clearly established a link between vascular calcification and bone metabolism. However, our understanding of the factors that contribute to vascular smooth muscle cell calcification in end-stage renal disease remains incomplete.


CONCLUSIONS
Systematic studies are required that integrate epidemiological studies to identify risk factors with in-vitro experiments to investigate mechanisms leading to vascular smooth muscle cell calcification in response to these factors. Animal and clinical studies can subsequently be used to assess how modifying risk factors under the complex physiological conditions of end-stage renal disease impacts on vessel wall health.
Shanahan
Catherine M
CM
Department of Medicine, University of Cambridge, Cambridge, UK. cs131@mole.bio.cam.ac.uk
D000818:Animals; D002114:Calcinosis / Q000209:etiology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications*; D014652:Vascular Diseases / Q000209:etiology