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Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification

Atherosclerosis Research Center and Burns and Allen Research Institute (T.M.D., P.K.S., T.B.R.), Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center and David Geffen School of Medicine at the University of California Los Angeles (UCLA), Los Angeles, California 90048; Division of Endocrinology, Diabetes, Metabolism, and Nutrition (L.A.F.), Department of Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905; Division of Endocrinology and Metabolism (D.I.), Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, Tokushima 770-8503, Japan; Department of Pathology and Laboratory Medicine (J.-H.Q., M.C.F.), David Geffen School of Medicine at UCLA, Los Angeles, California 90095; and Division of Cardiology (R.C.D.), Department of Medicine, Harbor-UCLA Research and Education Institute, Torrance, California 90512

Correspondence: Address all correspondence and requests for reprints to: Tripathi B. Rajavashisth, Ph.D., Atherosclerosis Research Center, Davis Research Building, Room 1062, Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center and David Geffen School of Medicine at University of California, Los Angeles, 8700 Beverly Boulevard, Los Angeles, California 90048-1865. E-mail: rajavashisth{at}cshs.org

Pathologists have recognized arterial calcification for over a century. Recent years have witnessed a strong resurgence of interest in atherosclerotic plaque calcification because it: 1) can be easily detected noninvasively; 2) closely correlates with the amount of atherosclerotic plaque; 3) serves as a surrogate measure for atherosclerosis, allowing preclinical detection of the disease; and 4) is associated with heightened risk of adverse cardiovascular events. There are two major types of calcification in arteries: calcification of the media tunica layer (sometimes called Mönckeberg’s sclerosis), and calcification within subdomains of atherosclerotic plaque within the intimal layer of the artery. There are important similarities and differences between these two entities. Of particular interest are increasing parallels between cellular and molecular features of arterial calcification and bone biology, and this has led to accelerating interest in understanding how and why bone-like mineral deposits may form in arteries. Here, we review the two major pathological types of arterial calcification, the proposed models of calcification, and endocrine and genetic determinants that affect arterial calcification. In addition, we highlight areas requiring further investigation.

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