Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1161-1170
Published online before print May 20, 2004, doi: 10.1161/01.ATV.0000133194.94939.42
Published online before print May 20, 2004, doi: 10.1161/01.ATV.0000133194.94939.42
© 2004 American Heart Association, Inc.
Brief Reviews |
Vascular Calcification
Mechanisms and Clinical Ramifications
From the Departments of Medicine (M.A., Y.T., L.L.D.) and Physiology (L.L.D.), The David Geffen School of Medicine at University of California, Los Angeles, Calif.
Correspondence to Dr Linda L. Demer, 47-123 CHS, David Geffen School of Medicine at UCLA, 10833 LeConte Ave, Los Angeles, CA 90095-1679. E-mail Ldemer{at}mednet.ucla.edu
Vascular calcification, long thought to result from passive degeneration, involves a complex, regulated process of biomineralization resembling osteogenesis. Evidence indicates that proteins controlling bone mineralization are also involved in the regulation of vascular calcification. Artery wall cells grown in culture are induced to become osteogenic by inflammatory and atherogenic stimuli. Furthermore, osteoclast-like cells are found in calcified atherosclerotic plaques, and active resorption of ectopic vascular calcification has been demonstrated. In general, soft tissue calcification arises in areas of chronic inflammation, possibly functioning as a barrier limiting the spread of the inflammatory stimulus. Atherosclerotic calcification may be one example of this process, in which oxidized lipids are the inflammatory stimulus. Calcification is widely used as a clinical indicator of atherosclerosis. It progresses nonlinearly with time, following a sigmoid-shaped curve. The relationship between calcification and clinical events likely relates to mechanical instability introduced by calcified plaque at its interface with softer, noncalcified plaque. In general, as calcification proceeds, interface surface area increases initially, but eventually decreases as plaques coalesce. This phenomenon may account for reports of less calcification in unstable plaque. Vascular calcification is exacerbated in certain clinical entities, including diabetes, menopause, and osteoporosis. Mechanisms linking them must be considered in clinical decisions. For example, treatments for osteoporosis may have unanticipated effects on vascular calcification; the converse also applies. Further understanding of processes governing vascular calcification may yield new therapeutic options for vascular disease.
Vascular calcification involves a complex biomineralization process that resembles osteogenesis. It is regulated by bone proteins and osteoblast-like cells found in the artery wall. Understanding its mechanism has implications for management of vascular disease, particularly in the context of bone disease.
Key Words: calcification • atherosclerosis • inflammation • bone • vascular
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