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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1162-1167.)
© 1999 American Heart Association, Inc.

Vascular Biology

Proteoglycans Contribution to Association of Lp(a) and LDL With Smooth Muscle Cell Extracellular Matrix

Ulf Lundstam; Eva Hurt-Camejo; Gun Olsson; Peter Sartipy; Germán Camejo; Olov Wiklund

From the Wallenberg Laboratory, Sahlgren's University Hospital, Göteborg, S-41345, Sweden (U.L., E.H.-C., G.O., P.S., G.C., O.W.); and the Astra Hässle AB, Preclinical Research Laboratories, Mölndal, S-431 83, Sweden (G.C.).

Correspondence to Germán Camejo, Astra Hässle AB, Preclinical Research Laboratories, Mölndal, S-431 83, Sweden. E-mail german.camejo{at}hassle.se.astra.com

Abstract—Lp(a) interference with fibrinolysis could contribute to atherothrombosis. Additionally, accumulation of Lp(a) and LDLs, could lead to cholesterol deposition and foam cell formation in atherogenesis. The interactions between Lp(a) and LDL could cause their entrapment in the extracellular matrix of lesions. We found that association of Lp(a) with matrix secreted by cultured human arterial smooth muscle cells increased 2 to 3 times the subsequent specific binding of radioactive LDL. Chondroitin sulfate proteoglycans seem responsible for formation of the specific matrix-Lp(a) and matrix-LDL aggregates. The proteoglycans appeared also to participate in a cooperative increase of radioactive LDL binding to matrix pretreated with Lp(a). In the matrix preincubated with LDL, 50% of the additional lipoprotein was bound by ionic interactions. In the matrix preincubated with Lp(a), 20% of the additional LDL was held by ionic bonds, and the rest was held by strong nonionic associations. Binding analysis in physiological solutions confirmed that chondroitin sulfate-rich proteoglycans from the smooth muscle cell matrix have a high affinity for Lp(a) and LDL. The results provide an explanation to the observed localization of Lp(a) and LDL in the extracellular matrix of arterial lesions and suggest a mechanism for their cooperative accumulation there.

Key Words: lipoprotein(a) • LDL • smooth muscle cells • extracellular matrix

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