Proteoglycans contribution to association of Lp(a) and LDL with smooth muscle cell extracellular matrix

Lp(a) interference with fibrinolysis could contribute to atherothrombosis. Additionally, accumulation of Lp(a) and LDLs, could lead to cholesterol dep osition and foam cell formation in atherogenesis. The interactions between Lp(a) and LDL could cause their entrapment in the extracellular matrix of l esions. We found that association of Lp(a) with matrix secreted by cultured human arterial smooth muscle cells increased 2 to 3 times the subsequent s pecific binding of radioactive LDL. Chondroitin sulfate proteoglycans seem responsible for formation of the specific matrix-lp(a) and matrix-LDL aggre gates. The proteoglycans appeared also to participate in a cooperative incr ease of radioactive I;DL binding to matrix pretreated with Lp(a). In the ma trix preincubated with LDL, approximate to 50% of the additional Lipoprotei n was bound by ionic interactions. In the matrix preincubated with Lp(a), 2 0% of the additional LDL was held by ionic bonds, and the rest was held by strong nonionic associations. Binding analysis in physiological solutions c onfirmed 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 extracell ular matrix of arterial lesions and suggest a mechanism for their cooperati ve accumulation there.