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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:606.)
© 2008 American Heart Association, Inc.

Editorials

Vascular Calcification in Homozygote Familial Hypercholesterolemia

Joel D. Morrisett; Kasey C. Vickers

From the Departments of Medicine and Biochemistry, Baylor College of Medicine, Houston, Tex.

Correspondence to Joel Morrisett, Departments of Medicine and Biochemistry, Baylor College of Medicine, Brown-Fondren Bldg, A601, Houston, TX 77030. E-mail morriset@bcm.tmc.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Awan and coworkers¹ describe the study of 25 homozygous familial hypercholesterolemic (FH) patients aged 5 to 54 years. Eighteen of the patients had aortic calcification scores >1000. The inference of this study is a strong linkage between homozygous FH and premature aortic calcification. Bazan et al² have recently described the age dependence of aortic calcification (Agatston units): 12.6±12.3 for <50 years, 14.6±8.2 for 50 to 59 years; 276±120 for 60 to 69 years, 1382±366 for 70 to 79 years, and 3889±778 for 80 years. Hence most of the elevated calcification observed in the Awan cohort is not attributable to age and may be attributable to hypercholesterolemia. The apparent connection between premature aortic calcification and hypercholesterolemia begs for a mechanistic explanation. One explanation is that hypercholesterolemia may ultimately stimulate transdifferentiation of atherosclerosis-associated cells into osteoblast-like calcifying vascular cells,^3,4,5 an irreversible process leading to arterial wall calcification. Hypercholesterolemia has been shown to accelerate vascular calcification through Vitamin D and its metabolites.⁶ 1,25-Dihydroxyvitamin D₃, is a Vitamin D metabolite known to induce calcium uptake and in vitro osteogenesis in vascular smooth muscle cells.^7,8 Additionally, hypercholesterolemia-induced oxidative stress may play a significant role in the generation of modified LDL and oxidized lipid products, which are also thought to induce differentiation of calcifying vascular cells resulting in vascular calcification.^6,9,10

See accompanying article on page 777

A second explanation could be a hypercholesterolemia-induced increase in osteoprotegerin, a decoy protein that hijacks RANK ligand (RANKL), preventing . . . [Full Text of this Article]

Related Article:

Vascular Calcifications in Homozygote Familial Hypercholesterolemia

Z. Awan, K. Alrasadi, G.A. Francis, R.A. Hegele, R. McPherson, J. Frohlich, D. Valenti, B. de Varennes, M. Marcil, C. Gagne, J. Genest, and P. Couture
Arterioscler Thromb Vasc Biol 2008 28: 777-785. [Abstract] [Full Text] [PDF]