Influence of plasma lipid and LDL-subfraction profile on the interaction between low density lipoprotein with human arterial wall proteoglycans.

Low density lipoprotein (LDL) is known to bind to arterial wall proteoglycans (APG), an interaction which may initiate cholesterol deposition in the arterial wall. The objective of this study was to determine whether a predominance of small, dense LDL (LDL-III, d = 1.044-1.063 g/ml) in the circulation in association with an atherogenic lipoprotein phenotype (ALP) (i.e. LDL-III > 100 mg/dl, an elevated plasma triglyceride and a low high density lipoprotein cholesterol) alters LDL reactivity towards APG. Total LDL (d = 1.019-1.063 g/ml) was isolated from 59 patients undergoing coronary angiography (39 males and 20 females) and the LDL subfraction profile determined by non-equilibrium density gradient centrifugation. A binding assay was developed in which total LDL (0.1 mg/ml apo LDL) was mixed with a standard preparation of APG containing 2.5 micrograms/ml chondroitin sulphate and the extent of APG-LDL complex formation followed by absorbance measurement and the amount of precipitated LDL cholesterol. APG-LDL complex formation was positively associated with (a) the percentage of LDL-III within total LDL (r = 0.48, P < 0.0001); (b) the plasma triglyceride level (r = 0.27, P < 0.04); and negatively associated with (a) the percentage of the buoyant LDL-I (d = 1.019-1.033 g/ml)(r = -0.47, P < 0.0001); and (b) the HDL cholesterol concentration (r = -0.37, P < 0.004). There was no association with the percentage of the major LDL species LDL-II. When the patients were divided according to the presence or absence of an ALP i.e. LDL-III greater or less than 100 mg/dl respectively, proteoglycan-LDL complex formation was significantly higher in the former compared to the latter group of patients (P < 0.0001). This study therefore provides evidence that the extent of the interaction of LDL with APG varies considerably between individuals and is enhanced in the presence of ALP. It is postulated that the increased atherogenicity associated with ALP may in part be due to prolonged and enhanced retention of LDL by the arterial wall.