Vascular calcification in homozygote familial hypercholesterolemia.

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 1,25Dihydroxyvitamin D3, is a Vitamin D metabolite known to induce calcium uptake and in vitro osteogenesis in vascular smooth muscle cells.7,8 Additionally, hypercholesterolemiainduced 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