The Proteoglycan Decorin Links Low Density Lipoproteins with Collagen Type I

Abstract

Decorin is a small dermatan sulfate-rich proteoglycan which binds to collagen type I in vitro and in vivo. In atherosclerotic lesions the contents of low density lipoprotein (LDL), decorin, and collagen type I are increased, and ultrastructural studies have suggested an association between LDL and collagen in the lesions. To study interactions between LDL, decorin, and collagen type I, we used solid phase systems in which LDL was coupled to a Sepharose column, or in which LDL, decorin, or collagen type I was attached to microtiter wells. The interaction between LDL and decorin in the fluid phase was evaluated using a gel mobility shift assay. We found that LDL binds to decorin by ionic interactions. After treatment with chondroitinase ABC, decorin did not bind to LDL, showing that the glycosaminoglycan side chain of decorin is essential for LDL binding. Acetylated and cyclohexanedione-treated LDL did not bind to decorin, demonstrating that both lysine and arginine residues of apoB-100 are necessary for the interaction. When collagen type I was attached to the microtiter plates, only insignificant amounts of LDL bound to the collagen. However, if decorin was first allowed to bind to the collagen, binding of LDL to the decorin-collagen complexes was over 10-fold higher than to collagen alone. Thus, decorin can link LDL with collagen type I in vitro, which suggests a novel mechanism for retention of LDL in collagen-rich areas of atherosclerotic lesions.Deposition of low density lipoproteins (LDL) 1 in the extracellular matrix of the arterial intima is an important step in the development of atherosclerosis (1). LDL interacts with the various components of the extracellular matrix. These components include proteoglycans (PG), elastin, and collagen. Binding of LDL to PG has been characterized in detail (2). Interaction between LDL and elastin has also been reported (3). In contrast, interaction between native LDL and collagen has received little attention (4, 5).Collagen is the major connective tissue component of atherosclerotic arteries, comprising up to 40% of the total protein in fibrous plaques and 60% in advanced lesions (6). Most of the collagen (50 -75%) in a normal artery or in a diseased intima is of type I (7-9). Immunofluorescence microscopy has located LDL along collagen fibers in atherosclerotic lesions (10, 11).Electron microscopic and immunoelectron microscopic studies have also suggested an association between LDL and collagen in the arterial intima (12)(13)(14).Decorin (15) is a small PG having a core protein with a molecular mass of 45 kDa and a single dermatan sulfate-rich side chain. Decorin has been shown to bind to and modify the fibrillar structure of collagen type I (16, 17), and importantly, to co-localize with collagen type I in primary atherosclerotic plaques (18).The present study concerns the interaction between native LDL and collagen type I in the absence and presence of decorin. In the absence of decorin, there was no significant interaction between LDL and collagen type I. However, w...

Phospholipids in Amelogenesis and Dentinogenesis

“…They may be involved in the transport of collagen fibrils from the proximal predentin, the place where they are secreted, to the distal part, where mineralization occurs. It is possible that PGs together with lipoproteins play roles in the fibrillation process of collagen, as is the case in vitro (Pentikäinen et al, 1997). Liposomes, on the other hand, as observed in many areas in our predentin sections, may contribute to calcium transport toward the mineralization front.…”

Ultrastructural Localization of Secretory Type II Phospholipase A 2 in Atherosclerotic and Nonatherosclerotic Regions of Human Arteries

“…[52][53][54] The interaction between decorin or biglycan and collagen type I has been studied extensively in vitro and in vivo. [55][56][57][58] Both proteoglycans colocalize with collagen types I and III in atherosclerotic plaques. 59 Furthermore, decorin and biglycan have chondroitin/dermatan sulfate GAG chains that can potentially bind both LDL and snpPLA 2 .…”

Proteoglycans in Dentinogenesis

“…The interaction between low-density lipoproteins (LDL) and PGs contributes to the mineralization of atherosclerotic lesions (Jorge-Herrero et al, 1991;Sanbandam et al, 1991). In addition, it has been established that the PG decorin links LDL with collagen type I (Pentikainen et al, 1997). It should be noted that the phospholipase A2-modified LDL has about twice the affinity for the sulphated PG than the undegraded LDL (Sartipy et al, 1999).…”