Association of apo B lipoproteins with arterial proteoglycans: Pathological significance and molecular basis

Retention of apo B-100 lipoproteins, low density lipoprotein (LDL) and probably lipoprotein(a), Lp(a), by intima proteoglycans (PGs) appears to increase the residence time needed for their structural, hydrolytic and oxidative modifications. If the rate of LDL entry exceeds the tissue capacity to eliminate the modified products, this process may be a contributor to atherogenesis and lesion advancement. LDL binds to PGs of the intima, by association of specific positive segments of the apo B-100 with the negatively-charged glycosaminoglycans (GAGs) made of chondroitin sulfate (CS), dermatan sulfate (DS) and probably heparan sulfate (HS). Small, dense LDL has a higher affinity for CS-PGs than large buoyant particles, probably because they expose more of the segments binding the GAGs than larger LDL. PGs cause irreversible structural alterations of LDL that potentiate hydrolytic and oxidative modifications. These alterations also increase LDL uptake by macrophages and smooth muscle cells. These in vitro data suggest that part of the atherogenicity of LDL may depend on its tendency to form complexes with arterial PGs in vivo. Ex vivo results support this hypothesis. Subjects with coronary heart disease have LDL with significantly higher affinity for arterial PGs. This is also a characteristic of subjects with the atherogenic lipoprotein phenotype, with high levels of small, dense LDL. The LDL-PG affinity, however can be modified by dietary or pharmacological interventions that change the composition and size of LDL. Lesion-prone intima contain PGs with a high affinity for LDL. Increased LDL entrapment at these sites may be a key step in a cyclic atherogenic process. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.