Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:680-687
© 1997 American Heart Association, Inc.
Articles |
Lipid Oxidation Products Have Opposite Effects on Calcifying Vascular Cell and Bone Cell Differentiation
A Possible Explanation for the Paradox of Arterial Calcification in Osteoporotic Patients
Presented in part at the 68th Scientific Sessions of the American Heart Association, Anaheim, Calif, November 13-16, 1995.
From the Division of Cardiology, Department of Medicine (F.P., A.D.M., J.B., Y.T., L.L.D.) and Department of Pathology (N.L., A.D.W., J.A.B.), University of California at Los Angeles School of Medicine.
Correspondence to F. Parhami, PhD, Division of Cardiology, UCLA School of Medicine, 47-123 Center for the Health Sciences, 10833 Le Conte Ave, Los Angeles, CA 90095. E-mail fparhami{at}medicine.medsch.ucla.edu
Abstract Atherosclerotic calcification and osteoporosis often
coexist in patients, yielding formation of bone mineral in vascular
walls and its simultaneous loss from bone. To assess the
potential role of lipoproteins in both processes, we examined the
effects of minimally oxidized low-density lipoprotein (MM-LDL) and
several other lipid oxidation products on calcifying vascular cells
(CVCs) and bone-derived preosteoblasts MC3T3-E1. In CVCs, MM-LDL but
not native LDL inhibited proliferation, caused a dose-dependent
increase in alkaline phosphatase activity, which is a marker of
osteoblastic differentiation, and induced the formation of extensive
areas of calcification. Similar to MM-LDL, oxidized
1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine
(ox-PAPC) and the isoprostane 8-iso prostaglandin
E2 but not PAPC or isoprostane 8-iso
prostaglandin F2
induced
alkaline phosphatase activity and differentiation of CVCs. In contrast,
MM-LDL and the above oxidized lipids inhibited differentiation of the
MC3T3-E1 bone cells, as evidenced by their stimulatory effect on
proliferation and their inhibitory effect on the induction
of alkaline phosphatase and calcium uptake. These results suggest that
specific oxidized lipids may be the common factors underlying the
pathogenesis of both atherosclerotic calcification and osteoporosis.
Key Words: calcification • atherosclerosis • oxidized lipids • calcifying vascular cells • alkaline phosphatase
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S. Jono, C. Peinado, and C. M. Giachelli Phosphorylation of Osteopontin Is Required for Inhibition of Vascular Smooth Muscle Cell Calcification J. Biol. Chem., June 23, 2000; 275(26): 20197 - 20203. [Abstract] [Full Text] [PDF]
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F. Parhami, Y. Tintut, A. Ballard, A. M. Fogelman, and L. L. Demer Leptin Enhances the Calcification of Vascular Cells : Artery Wall as a Target of Leptin Circ. Res., May 11, 2001; 88(9): 954 - 960. [Abstract] [Full Text] [PDF]
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