Interaction of Low Density Lipoproteins with Arterial Constituents: Its Relationship with Atherogenesis

Thermotropic Changes in the Surface Structure of Lipoprotein B from Human‐Plasma Low‐Density Lipoproteins

“…The protein-bound spin label shows two spectral components arising from weakly and tightly immobilized binding sites, the ratio of the former to the latter increasing strongly between 25 and 30 "C concomitantly with a decrease in the separation of the two signals. The combined results indicate reversible changes in the fine structure involving both protein and polar lipids at the surface of lipoprotein B which correlate to the thermotropic transition of the apolar lipids in the particle core.The physiological role of low-density lipoproteins as the major transport vehicles of cholesterol in human blood [I] and their apparent involvement in the pathophysiology of atherosclerosis [2,3] has stimulated numerous studies directed towards an elucidation of their structure. Most of the existing evidence from chemical and physico-chemical investigations (for a recent review see Laggner [4]) supports a structural model in which the apolar constituents, cholesteryl esters and triglycerides, form the particle core surrounded by the amphiphilic moieties, phospholipids, unesterified cholesterol and protein, forming the external shell.…”

“…By calorimetric [ S , 61, X-ray [5,7 -91 and spectroscopic techniques [lo, 111 it has been shown that the molecular packing of the cholesteryl esters and triglycerides within the core undergoes a reversible order-disorder transition at temperatures between 15 and 40 "C. Since the temperature course of the transition varies between individuals it has been suggested that this effect might have significance in the catabolism of low-density lipoproteins [6]. Therefore, and in view of the current concepts of recognition, internalization and degradation by target cells [12,3 31, it seems of particular interest to investigate whether this transition affects the surface structure possibly making it recognizable also to receptor binding sites and enzymes involved in binding and degradation of low-density lipoproteins.Previous studies [14,15] have indicated a temperature sensitivity of the optical activity which has been related to the protein conformation; it was suggested by Chi Chen and Kane [16], however, that this effect could be ascribed in substantial part to changes in the lipid structure. Thus the structural nature of these changes remained unclear.…”

“…The physiological role of low-density lipoproteins as the major transport vehicles of cholesterol in human blood [I] and their apparent involvement in the pathophysiology of atherosclerosis [2,3] has stimulated numerous studies directed towards an elucidation of their structure. Most of the existing evidence from chemical and physico-chemical investigations (for a recent review see Laggner [4]) supports a structural model in which the apolar constituents, cholesteryl esters and triglycerides, form the particle core surrounded by the amphiphilic moieties, phospholipids, unesterified cholesterol and protein, forming the external shell.…”