title: Oxidized LDL bind to nonproteoglycan components of smooth muscle extracellular matrices.
abstract: 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) = approximately 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.
authors.affiliation: Departments of Pathology, Division of Metabolism, Endocrinology, and Nutrition, School of Medicine, 1959 NE Pacific, BB-928 Health Sciences, Box 356426, University of Washington, Seattle, WA 98195-6426, USA.
authors.forename: M Y
authors.initials: MY
authors.lastname: Chang
authors.forename: S
authors.initials: S
authors.lastname: Potter-Perigo
authors.forename: T N
authors.initials: TN
authors.lastname: Wight
authors.forename: A
authors.initials: A
authors.lastname: Chait
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D019765:Chondroitin ABC Lyase / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D003851:Deoxyribonucleases / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D019763:Heparin Lyase / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008254:Macaca nemestrina; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000378:metabolism; D010316:Particle Size; D011402:Pronase / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism
chemical_list: D002614:Chelating Agents; D008077:Lipoproteins, LDL; D011509:Proteoglycans; C099252:oxidized low density lipoprotein; D003300:Copper; D002809:Chondroitin Sulfates; D004492:Edetic Acid; D003851:Deoxyribonucleases; D010196:Pancreatic Elastase; D014357:Trypsin; D011402:Pronase; D019765:Chondroitin ABC Lyase; D019763:Heparin Lyase