The composition, structural properties and binding of very-low-density and low-density lipoproteins to the LDL receptor in normo- and hypertriglyceridemia: relation to the apolipoprotein E phenotype

Abstract

The composition, apolipoprotein structure and lipoprotein binding to the LDL receptor were studied for very-low-density (VLDL) and low-density lipoprotein (LDL) particles isolated from subjects with apoE phenotype E3/3 (E3), E2/2 or E2/3 (E2+) and E3/4 or E4/4 (E4+) and a wide range of plasma triglyceride (TG) contents. The data combined for all three phenotype groups can be summarized as follows. (i) A decrease in accessibility of VLDL tryptophan residues to I- anions with a decrease in tryptophan surface density, concomitant with an increase in VLDL dimensions, reflects the increased efficiency of protein-protein interactions. (ii) A gradual increase in the quenching constant for LDL apoB fluorescence with an increase in TG/cholesterol (Chol) ratio reflects the 'freezing' effect of Chol molecules on apoB dynamics. (iii) Different mechanisms specific for a particular lipoprotein from E3/3 or E2/3 subjects are responsible for apoE-mediated VLDL binding and apoB-mediated LDL binding to the LDL receptor in a solid-phase binding assay. (iv) The 'spacing' effect of apoC-III molecules on apoE-mediated VLDL binding results in a decrease in the number of binding sites. (v) The maximum of the dependence of the LDL binding affinity constant on relative tryptophan density corresponds to LDL intermediate size. VLDL particles from hypertriglyceridemic E2/3 heterozygotic individuals had remnant-like properties (increased cholesterol, apoE and decreased apoC-III content) while their binding efficiency was unchanged. Based on the affinity constant value and LDL-Chol content, increased competition between VLDL and LDL for the binding to the LDL receptor upon increase in plasma TG is suggested, and LDL from hypertriglyceridemic E3/3 homozygotic individuals is the most efficient competitor.

Apolipoprotein E Phenotype in Demented Patients in Greek Population

“…Apolipoprotein E (ApoE), a plasma protein that binds to low-density lipoprotein receptor (LDL-R), has been involved in the transport of cholesterol and its metabolism (Dergunov et al, 2005;Ji et al, 2003). It also seems to play a role in the growth and regeneration of peripheral and central nervous tissues during development and following injury (Czapiga & Colton, 2003).…”

“…The E2 isoform carries cysteine at both positions, whereas E4 carries arginines at both positions. The presence of at least one copy of Apo e2 alléle has been associated with lower risk of coronary heart disease (Dergunov et al, 2005) and also with higher levels of plasma ApoE and lower plasma Chol, LDL-Chol when compared to E3 homozygotes, whereas the E4 isoform seems to be involved in the late-onset of Alzheimer's disease (Strittmatter et al, 1993a,b;Corder et al, 1993).…”

Επίδραση Της Θεραπείας Με Στατίνη Σε Μεταβολικές Παραμέτρους Σε Ασθενείς Με Πρωτοπαθή Δυσλιπιδαιμία

“…Η ανεξάρτητη συσχέτιση ανάμεσα στη μείωση των επιπέδων των TG και στην αντίστοιχη μείωση της apoC-III είναι ένα άλλο σημαντικό εύρημα της παρούσας μελέτης. Η apoC-III διαδραματίζει σημαντικό ρόλο στον καταβολισμό των πλούσιων σε TG λιποπρωτεϊνών, καθώς αποτελεί ένα ισχυρό αναστολέα της LPL, του ενζύμου που είναι υπεύθυνο για τη λιπόλυση των τριγλυκεριδίων των VLDL και των χυλομικρών570,667 . Πράγματι, τα αυξημένα επίπεδα της apoC-III έχουν συσχετισθεί με αυξημένα επίπεδα TG570,668 .…”