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, hydrolyti c and oxidative modifications. If the rate of LDL entry exceeds the ti ssue capacity to eliminate the modified products, this process may be a contributor to atherogenesis and lesion advancement. LDL binds to PG s of the intima, by association of specific positive segments of the a po 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 l arge buoyant particles, probably because they expose more of the segme nts binding the GAGs than larger LDL. PGs cause irreversible structura l alterations of LDL that potentiate hydrolytic and oxidative modifica tions. These alterations also increase LDL uptake by macrophages and s mooth muscle cells. These in vitro data suggest that part of the ather ogenicity of LDL may depend on its tendency to form complexes with art erial PGs in vivo. Ex vivo results support this hypothesis. Subjects w ith 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 LD L. The LDL-PG affinity, however can be modified by dietary or pharmaco logical interventions that change the composition and size of LDL. Les ion-prone intima contain PGs with a high affinity for LDL. Increased L DL entrapment at these sites may be a key step in a cyclic atherogenic process. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.