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Originally published In Press as doi:10.1074/jbc.M508565200 on September 6, 2005
J. Biol. Chem., Vol. 280, Issue 45, 37449-37454, November 11, 2005
Decrease in pH Strongly Enhances Binding of Native, Proteolyzed, Lipolyzed, and Oxidized Low Density Lipoprotein Particles to Human Aortic Proteoglycans*
Mia Sneck,
Petri T. Kovanen, and
Katariina Öörni1
From the
Wihuri Research Institute, Kalliolinnantie 4, FIN-00140 Helsinki, Finland
Binding of low density lipoprotein (LDL) to proteoglycans and modification of LDL are key processes in atherogenesis. Recently, it has been demonstrated that during atherogenesis the extracellular pH of atherosclerotic lesions decreases. We have examined the effect of the decreased pH on the binding of LDL to human aortic proteoglycans. The binding of native, oxidized, proteolyzed ( -chymotrypsin-treated), or lipolyzed (sphingomyelinase- or phospholipase A2-treated) LDL particles to proteoglycans were measured in microtiter well assays at pH 5.57.5. We found that the lower the pH, the higher the amount of binding of LDL to proteoglycans. At the lowest pH tested (pH 5.5), the amounts of proteoglycan-bound native, proteolyzed, sphingomyelinase-, and phospholipase A2-treated LDL were 20-, 23-, 30-, and 37-fold higher, respectively, than at pH 7.5. Interestingly, although oxidized LDL failed to bind to proteoglycans at neutral pH, there was significant binding at acidic pH. Binding of native and modified LDL to proteoglycans at pH 5.5 was blocked by 1 M NaCl, indicating that at neutral pH LDL binds to proteoglycans via ionic interactions. Inhibition of this binding by acetylation and cyclohexanedione treatment of LDL showed that the positively charged amino acids of apolipoprotein B-100, lysine, and arginine, respectively, mediated the ionic interaction. Taken together, our results suggest that in areas of atherosclerotic arterial intima where the extracellular pH decreases, retention of LDL by proteoglycans is enhanced, leading to extracellular accumulation of LDL and progression of the disease.
Received for publication, August 4, 2005
, and in revised form, September 2, 2005.
* This work was supported by a grant from the Academy of Finland (to K.Ö.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 To whom correspondence should be addressed. Tel.: 358-9-681-411; Fax: 358-9-637-476; E-mail: kati.oorni{at}wri.fi.

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Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.
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