INSOLUBLE COMPLEX-FORMATION BETWEEN LDL AND ARTERIAL PROTEOGLYCANS INRELATION TO SERUM-LIPID LEVELS AND EFFECTS OF LIPID-LOWERING DRUGS

Lipoprotein deposition and increased intimal proteoglycans are charact eristics of the atherosclerotic lesion in which low density lipoprotei ns (LDL) bind with high affinity to proteoglycans. The affinity of LDL to proteoglycans is dependent on its structural and compositional cha racteristics. This study investigated the relationship between serum l ipid levels and LDL-proteoglycan reactivity. We also analyzed how lipi d-lowering drugs affect this interaction. Patients with moderate hyper cholesterolemia (n = 147) were randomized to pravastatin 40 mg o.d., g emfibrozil 600 mg b.i.d., gemfibrozil + pravastatin (same doses) or pl acebo. LDL reactivity with proteoglycans was analyzed by precipitation of serum with isolated human arterial proteoglycans. Reactivity was d etermined as amount of precipitated cholesterol or apolipoprotein (ape ) B. Under the conditions used, 53% of the LDL cholesterol and 29% of serum apo B were precipitated. There were strong correlations between precipitated LDL and serum levels of cholesterol, LDL or apo B. No cor relations were found with serum lipoprotein(a) (Lp(a)) levels. During pravastatin treatment, cholesterol was reduced by 26.5% and triglyceri des by 9.8%. During gemfibrozil treatment corresponding figures were 1 6.8 and 40.2, and for the combined treatment, 27.5% and 34.2%. On all treatments, the reactivity of LDL with proteoglycan was reduced. The e ffects were significantly larger in the groups treated with gemfibrozi l. This was correlated with the increase in high density lipoprotein ( HDL) during gemfibrozil treatment. In hypercholesterolemia, the reacti vity of LDL with proteoglycan is increased; treatment with lipid-lower ing drugs lowers this reactivity, the effect being greatest for gemfib rozil. This might be due to conformational changes of LDL during treat ment with gemfibrozil, unrelated to its lipid lowering effect. Since b inding of LDL to proteoglycans is central in atherogenesis, this may b e of importance for the role of gemfibrozil as an antiatherogenic drug .