Composition, morphology and distribution of high-density lipoproteins in plasma and peripheral lymph: effect of feeding cholesterol and saturated fat

In euthyroid dogs fed a diet rich in cholesterol and saturated fat, the cholesterol concentration in both plasma and peripheral lymph increased progressively with the appearance of HDLc (d 1.006-1.063). This HDLc fraction was heterogeneous and could be separated into 'slow' and 'fast' migrating fractions by Pevikon block electrophoresis. On SDS-polyacrylamide gel electrophoresis, plasma 'slow' HDLc was appreciably enriched in apolipoprotein (apo) E, while plasma and lymph 'fast' HDLc were apo E-poor. In contrast, no apo E was visible in lymph 'slow' HDLc in either plasma or lymph HDL2 fractions (d 1.087-1.21). The interstitial HDL fractions containing apo A-IV ('fast' HDLc and HDL2) were also rich in free cholesterol, implying that apo A-IV-containing particles are involved in reverse cholesterol transport. Plasma and peripheral lymph HDL2 and 'fast' HDLc cholesterol/protein ratios were not different, whereas lymph 'slow' HDLc was 24% that of plasma, indicating that interstitial 'slow' HDLc was poor in cholesterol compared to plasma. This marked reduction in lymph 'slow' HDLc cholesterol suggests that this particle was either selectively retarded from egress by the endothelial barrier, or that interstitial 'slow' HDLc represents a depleted particle involved in the delivery of cholesterol to peripheral tissues. These findings taken together support the hypothesis that interstitial 'slow' HDLc may represent a particle involved in cholesterol ester delivery, in contrast with HDL2 and 'fast' HDLc, which could serve as an efflux acceptor of tissue free cholesterol. This study demonstrates significant heterogeneity of interstitial peripheral lymph lipoproteins compared to plasma lipoproteins, and indicates selective distribution of these particles in the extravascular space.