This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Doherty, T. M. Articles by Rajavashisth, T. B. Search for Related Content PubMed PubMed Citation Articles by Doherty, T. M. Articles by Rajavashisth, T. B.

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.

This article has been cited by other articles:

				M. Ohnishi, T. Nakatani, B. Lanske, and M. S. Razzaque In Vivo Genetic Evidence for Suppressing Vascular and Soft-Tissue Calcification Through the Reduction of Serum Phosphate Levels, Even in the Presence of High Serum Calcium and 1,25-Dihydroxyvitamin D Levels Circ Cardiovasc Genet, December 1, 2009; 2(6): 583 - 590. [Abstract] [Full Text] [PDF]

				A. N. Wade and M. P. Reilly Coronary Calcification in Chronic Kidney Disease: Morphology, Mechanisms and Mortality Clin. J. Am. Soc. Nephrol., December 1, 2009; 4(12): 1883 - 1885. [Full Text] [PDF]

				M. J. Blaha, M. J. Budoff, J. J. Rivera, R. Katz, D. H. O'Leary, J. F. Polak, J. Takasu, R. S. Blumenthal, and K. Nasir Relationship of Carotid Distensibility and Thoracic Aorta Calcification: Multi-Ethnic Study of Atherosclerosis Hypertension, December 1, 2009; 54(6): 1408 - 1415. [Abstract] [Full Text] [PDF]

				T. Nakatani, M. Ohnishi, and M. S. Razzaque Inactivation of klotho function induces hyperphosphatemia even in presence of high serum fibroblast growth factor 23 levels in a genetically engineered hypophosphatemic (Hyp) mouse model FASEB J, November 1, 2009; 23(11): 3702 - 3711. [Abstract] [Full Text] [PDF]

				S. Helas, C. Goettsch, M. Schoppet, U. Zeitz, U. Hempel, H. Morawietz, P. J. Kostenuik, R. G. Erben, and L. C. Hofbauer Inhibition of Receptor Activator of NF-{kappa}B Ligand by Denosumab Attenuates Vascular Calcium Deposition in Mice Am. J. Pathol., August 1, 2009; 175(2): 473 - 478. [Abstract] [Full Text] [PDF]

				J. Atkinson Age-related medial elastocalcinosis in arteries: mechanisms, animal models, and physiological consequences J Appl Physiol, November 1, 2008; 105(5): 1643 - 1651. [Abstract] [Full Text] [PDF]

				M. Gossl, U. I. Modder, E. J. Atkinson, A. Lerman, and S. Khosla Osteocalcin Expression by Circulating Endothelial Progenitor Cells in Patients With Coronary Atherosclerosis J. Am. Coll. Cardiol., October 14, 2008; 52(16): 1314 - 1325. [Abstract] [Full Text] [PDF]

				A. Fales-Williams, B. Sponseller, and H. Flaherty Idiopathic arterial medial calcification of the thoracic arteries in an adult horse J Vet Diagn Invest, September 1, 2008; 20(5): 692 - 697. [Abstract] [Full Text] [PDF]

				A. Heiss, T. Eckert, A. Aretz, W. Richtering, W. van Dorp, C. Schafer, and W. Jahnen-Dechent Hierarchical Role of Fetuin-A and Acidic Serum Proteins in the Formation and Stabilization of Calcium Phosphate Particles J. Biol. Chem., May 23, 2008; 283(21): 14815 - 14825. [Abstract] [Full Text] [PDF]

				P. Eller, K. Hochegger, G. M. Feuchtner, E. Zitt, I. Tancevski, A. Ritsch, F. Kronenberg, A. R. Rosenkranz, J. R. Patsch, and G. Mayer Impact of ENPP1 genotype on arterial calcification in patients with end-stage renal failure Nephrol. Dial. Transplant., January 1, 2008; 23(1): 321 - 327. [Abstract] [Full Text] [PDF]

				D. Vega, N. M. Maalouf, and K. Sakhaee The Role of Receptor Activator of Nuclear Factor-{kappa}B (RANK)/RANK Ligand/Osteoprotegerin: Clinical Implications J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4514 - 4521. [Abstract] [Full Text] [PDF]

				D. F. Kallmes, Y. H. Ding, D. Dai, R. Kadirvel, D. A. Lewis, and H. J. Cloft A New Endoluminal, Flow-Disrupting Device for Treatment of Saccular Aneurysms Stroke, August 1, 2007; 38(8): 2346 - 2352. [Abstract] [Full Text] [PDF]

				A. Simionescu, D. T. Simionescu, and N. R. Vyavahare Osteogenic Responses in Fibroblasts Activated by Elastin Degradation Products and Transforming Growth Factor-{beta}1: Role of Myofibroblasts in Vascular Calcification Am. J. Pathol., July 1, 2007; 171(1): 116 - 123. [Abstract] [Full Text] [PDF]

				G. D.M. Collett, A. P. Sage, J. P. Kirton, M. Y. Alexander, A. P. Gilmore, and A. E. Canfield Axl/Phosphatidylinositol 3-Kinase Signaling Inhibits Mineral Deposition by Vascular Smooth Muscle Cells Circ. Res., March 2, 2007; 100(4): 502 - 509. [Abstract] [Full Text] [PDF]

				W. Post, L. F. Bielak, K. A. Ryan, Y.-C. Cheng, H. Shen, J. A. Rumberger, P. F. Sheedy II, A. R. Shuldiner, P. A. Peyser, and B. D. Mitchell Determinants of Coronary Artery and Aortic Calcification in the Old Order Amish Circulation, February 13, 2007; 115(6): 717 - 724. [Abstract] [Full Text] [PDF]

				R. C. Christian, P. Y. Liu, S. Harrington, M. Ruan, V. M. Miller, and L. A. Fitzpatrick Intimal Estrogen Receptor (ER){beta}, But Not ER{alpha} Expression, Is Correlated with Coronary Calcification and Atherosclerosis in Pre- and Postmenopausal Women J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2713 - 2720. [Abstract] [Full Text] [PDF]

				D. V. Anand, A. Lahiri, E. Lim, D. Hopkins, and R. Corder The Relationship Between Plasma Osteoprotegerin Levels and Coronary Artery Calcification in Uncomplicated Type 2 Diabetic Subjects J. Am. Coll. Cardiol., May 2, 2006; 47(9): 1850 - 1857. [Abstract] [Full Text] [PDF]

				D. V. Anand, E. Lim, A. Lahiri, and J. J. Bax The role of non-invasive imaging in the risk stratification of asymptomatic diabetic subjects Eur. Heart J., April 2, 2006; 27(8): 905 - 912. [Abstract] [Full Text] [PDF]

				M. Morena, N. Terrier, I. Jaussent, H. Leray-Moragues, L. Chalabi, J.-P. Rivory, F. Maurice, C. Delcourt, J.-P. Cristol, B. Canaud, et al. Plasma Osteoprotegerin Is Associated with Mortality in Hemodialysis Patients J. Am. Soc. Nephrol., January 1, 2006; 17(1): 262 - 270. [Abstract] [Full Text] [PDF]

				D. Hamerman Osteoporosis and atherosclerosis: biological linkages and the emergence of dual-purpose therapies QJM, July 1, 2005; 98(7): 467 - 484. [Abstract] [Full Text] [PDF]

				P. Y. Liu, R. C. Christian, M. Ruan, V. M. Miller, and L. A. Fitzpatrick Correlating Androgen and Estrogen Steroid Receptor Expression with Coronary Calcification and Atherosclerosis in Men without Known Coronary Artery Disease J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1041 - 1046. [Abstract] [Full Text] [PDF]

				P.E. Norman and J.T. Powell Vitamin D, Shedding Light on the Development of Disease in Peripheral Arteries Arterioscler Thromb Vasc Biol, January 1, 2005; 25(1): 39 - 46. [Abstract] [Full Text] [PDF]