Abnormalities of low-density lipoprotein metabolism in patients with coronary artery disease.

Persistent Link:
http://hdl.handle.net/10150/185596
Title:
Abnormalities of low-density lipoprotein metabolism in patients with coronary artery disease.
Author:
Shi, Fang.
Issue Date:
1991
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Studies have shown that hypercholesterolemia is a risk for cardiovascular disease; however, some normocholesterolemic individuals still develop coronary atherosclerosis. This project was undertaken to investigate the association of abnormalities of low density lipoprotein (LDL) metabolism, in the absence of hypercholesterolemia, with the development of coronary artery disease (CAD). Mononuclear leukocytes (MNL), HL-60 cells and 1,25-dihydroxyvitamin D₃-induced HL-60 macrophages were used as model systems to study the effect of an altered LDL composition on cellular lipoprotein and sterol metabolism. LDL and MNL were isolated from patients with and without CAD. The mean rate of LDL degradation was 1.7-fold higher in CAD-MNL than in control-MNL (P < 0.05), independent of the LDL source. The increased LDL degradation rate in CAD-MNL appeared to be due to an increased LDL receptor activity of 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 by HL-60 cells and D₃-induced HL-60 macrophages. LDL from CAD patients (CAD-LDL) contained significantly less cholesteryl ester per particle than LDL from control subjects (Control-LDL). The ability of CAD-LDL and Control-LDL to regulate sterol and lipoprotein metabolism was compared in HL-60 cells. The results indicate that CAD-LDL exhibited reduced abilities to suppress receptor-mediated LDL degradation and to activate acyl-CoA:cholesterol acyltransferase as compared to Control-LDL. There was no significant difference in the rate of sterol synthesis between cells treated with CAD-LDL and Control-LDL. The data support the hypothesis that cholesteryl ester-poor CAD-LDL exhibits a decreased ability to down-regulate LDL receptor activity which could in part account for the observed increase in LDL degradation by MNL from CAD patients. A noncompetitive enzyme-linked immunosorbent assay (ELISA) was developed to measure plasma apolipoproteins (apo) A-I and B. The results indicate that a reduced plasma apo A-I level was associated with CAD patients even if there were no significant differences in the levels of high density lipoprotein cholesterol when compared with individuals without CAD.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Dissertations, Academic; Nutrition; Low density lipoproteins.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Nutritional Sciences; Graduate College
Degree Grantor:
University of Arizona
Advisor:
McNamara, Donald J.

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleAbnormalities of low-density lipoprotein metabolism in patients with coronary artery disease.en_US
dc.creatorShi, Fang.en_US
dc.contributor.authorShi, Fang.en_US
dc.date.issued1991en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractStudies have shown that hypercholesterolemia is a risk for cardiovascular disease; however, some normocholesterolemic individuals still develop coronary atherosclerosis. This project was undertaken to investigate the association of abnormalities of low density lipoprotein (LDL) metabolism, in the absence of hypercholesterolemia, with the development of coronary artery disease (CAD). Mononuclear leukocytes (MNL), HL-60 cells and 1,25-dihydroxyvitamin D₃-induced HL-60 macrophages were used as model systems to study the effect of an altered LDL composition on cellular lipoprotein and sterol metabolism. LDL and MNL were isolated from patients with and without CAD. The mean rate of LDL degradation was 1.7-fold higher in CAD-MNL than in control-MNL (P < 0.05), independent of the LDL source. The increased LDL degradation rate in CAD-MNL appeared to be due to an increased LDL receptor activity of 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 by HL-60 cells and D₃-induced HL-60 macrophages. LDL from CAD patients (CAD-LDL) contained significantly less cholesteryl ester per particle than LDL from control subjects (Control-LDL). The ability of CAD-LDL and Control-LDL to regulate sterol and lipoprotein metabolism was compared in HL-60 cells. The results indicate that CAD-LDL exhibited reduced abilities to suppress receptor-mediated LDL degradation and to activate acyl-CoA:cholesterol acyltransferase as compared to Control-LDL. There was no significant difference in the rate of sterol synthesis between cells treated with CAD-LDL and Control-LDL. The data support the hypothesis that cholesteryl ester-poor CAD-LDL exhibits a decreased ability to down-regulate LDL receptor activity which could in part account for the observed increase in LDL degradation by MNL from CAD patients. A noncompetitive enzyme-linked immunosorbent assay (ELISA) was developed to measure plasma apolipoproteins (apo) A-I and B. The results indicate that a reduced plasma apo A-I level was associated with CAD patients even if there were no significant differences in the levels of high density lipoprotein cholesterol when compared with individuals without CAD.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectDissertations, Academicen_US
dc.subjectNutritionen_US
dc.subjectLow density lipoproteins.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineNutritional Sciencesen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorMcNamara, Donald J.en_US
dc.contributor.committeememberWells, Michael A.en_US
dc.contributor.committeememberReid, Bobby L.en_US
dc.contributor.committeememberHowell, Wanda H.en_US
dc.contributor.committeememberBohnert, Hans J.en_US
dc.identifier.proquest9200045en_US
dc.identifier.oclc711786819en_US
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