Varied low density lipoprotein binding property of proteoglycans synthesized by vascular smooth muscle cells cultured on extracellular matrix.
Earlier we showed that the extracellular matrix (ECM) secreted by vascular cells modulated proteoglycan synthesis by vascular smooth muscle cells in culture and altered the proteoglycan characteristics. In this study, we tested the hypothesis that these ECM-mediated alterations increased the affinity of the proteoglycans for plasma low density lipoprotein (LDL). Newly synthesized proteoglycans were isolated from smooth muscle cells cultured on the ECMs secreted by vascular endothelial cells, smooth muscle cells, or THP-1 macrophages and their binding affinity for LDL determined. Proteoglycans from all cultures contained sub-fractions that bound LDL with low and high affinity. However, compared with the cells plated on the endothelial cell ECM, the cells plated on the smooth muscle cell ECM and macrophage ECM synthesized significantly more high affinity proteoglycans. Removal of collagen, elastin, and chondroitin sulfates from the smooth muscle cell ECM and chondroitin sulfates from the macrophage ECM increased the production of high affinity proteoglycans by 15-22%. However, neutralization of fibronectin from both ECMs decreased the high affinity proteoglycans by 20%. Removal of matrix-bound growth factors had no effect on the synthesis of high affinity proteoglycans. Compared with the low affinity proteoglycans, the high affinity proteoglycans were larger, more sulfated and contained higher proportions of chondritin sulfate, dermatan sulfate, and N-sulfated heparan sulfate chains. These results suggest that the ECM-mediated alterations in vascular smooth muscle cell proteoglycans may lead to increased deposition of LDL in the arterial wall.
Vijayagopal
Parakat
P
Section of Cardiology, Department of Medicine, Louisiana State University Health Sciences Center, 533 Bolivar Street, New Orleans, LA 70112, USA. pvijay@lsuhsc.edu
Menon
Pramod V
PV
D001667:Binding, Competitive; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000502:physiology; D003094:Collagen / Q000502:physiology; D004549:Elastin / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D011509:Proteoglycans / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*
D005353:Fibronectins; D008077:Lipoproteins, LDL; D011509:Proteoglycans; D002809:Chondroitin Sulfates; D003094:Collagen; D004549:Elastin; D007930:Leucine