Increased degradation of low density lipoproteins by mononuclear leukocytes associated with coronary artery disease.
Low density lipoprotein (LDL) and peripheral blood mononuclear leukocytes (MNL) were isolated from patients with (n = 11) and without (n = 11) angiographically documented coronary artery disease (CAD). LDL degradation rates in MNL were determined in vitro using both autologous and homologous LDL. The mean rate of LDL degradation was 1.7-fold higher in CAD-MNL than in control-MNL (P less than 0.05), independent of the LDL source. The increased LDL degradation rate in CAD-MNL appeared to be due to an increased receptor-mediated LDL degradation rate in CAD-MNL and not to an increased CAD-LDL interaction with the receptor since LDL isolated from patients with and without CAD had similar in vitro degradation rates in HL-60 cells and 1.25-dihydroxyvitamin D3-induced HL-60 macrophages. An increased ratio of apo B to cholesterol, specifically apo B to cholesteryl ester, was observed in LDL isolated from patients with CAD. LDL particles isolated from CAD patients contained 14.8% less cholesteryl ester than LDL from control subjects (P less than 0.01). The data suggest that CAD patients have an increased plasma LDL particle number even though they have similar plasma LDL-cholesterol levels as compared to control subjects. These data indicate that CAD patients with normal plasma LDL cholesterol levels have two metabolic abnormalities: an altered LDL composition resulting in particles with reduced cholesteryl ester content and an increased LDL catabolism resulting in an increased influx of LDL cholesterol into MNL; both of which may play a role in the development of coronary heart disease.
Shi
F
F
Department of Nutrition and Food Science, University of Arizona, Tucson 85721.
Hurst
P G
PG
McNamara
D J
DJ
D001055:Apolipoproteins B / Q000032:analysis; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002784:Cholesterol / Q000032:analysis; D003327:Coronary Disease / Q000097:blood*; D005260:Female; D006801:Humans; D007942:Leukemia, Experimental / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011973:Receptors, LDL / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000378:metabolism
D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D002784:Cholesterol; D002117:Calcitriol