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Journal of Lipid Research, Vol. 42, 824-833, May 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

Oxidized LDL bind to nonproteoglycan components of smooth muscle extracellular matrices

Correspondence to: Alan Chait, To whom correspondence should be addressed., achait{at}u.washington.edu (E-mail)

Arterial wall lipid retention is believed to be due primarily to ionic interactions between lipoproteins and proteoglycans. Thus, oxidized low density lipoproteins (LDL), with decreased positive charge relative to native LDL, should have decreased interaction with negatively charged proteoglycans. However, oxidized LDL does accumulate within arterial lesions. Therefore, this study investigated the binding of native and oxidized LDL to a complex smooth muscle extracellular matrix and the role of ionic charge interactions in their binding. LDL was modified with 2,2-azo-bis(2-amidinopropane)-2HCl, hypochlorite, soybean lipoxygenase, and phospholipase or copper sulfate. The extracellular matrix had 15- to 45-fold greater binding capacity for the different forms of oxidized LDL than for native LDL. However, the affinity of binding for all forms of oxidized LDL was high (K_a = 10-9 M) and was similar to that for native LDL. Preincubation of the lipoproteins with chondroitin sulfate decreased the binding of native LDL, but had no effect on the binding of oxidized LDL. Digestion of matrices with chondroitin ABC lyase and heparinase decreased the binding of native LDL, but increased the binding of oxidized LDL; matrix digestion with pronase or trypsin markedly reduced the binding of both native and oxidized LDL.

Thus, the binding of native LDL involves matrix proteoglycans, whereas the binding of oxidized LDL involves a nonproteoglycan component(s) of the matrix. The markedly enhanced retention of oxidized LDL compared with native LDL may play an important role in the progression of atherosclerosis. — Chang, M. Y., S. Potter-Perigo, T. N. Wight, and A. Chait. Oxidized LDL bind to nonproteoglycan components of smooth muscle extracellular matrices. J. Lipid Res. 2001. 42: 824;–833.

Supplementary key words: soybean lipoxygenase, hypochlorite, copper, glycosaminoglycan, chondroitin sulfate, chondroitin ABC lyase, heparinase, collagen, matrix

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