Increased degradation of low density lipoproteins by mononuclear leukocytes associated with coronary artery disease
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F Shi1, P G Hurst, D J McNamara
1Department of Nutrition and Food Science, University of Arizona, Tucson 85721.
Insights
Patients with coronary artery disease (CAD) exhibit increased low-density lipoprotein (LDL) degradation by immune cells, even with normal cholesterol levels. This suggests altered LDL metabolism contributes to heart disease development.
Area of Science:
- Cardiovascular Science
- Lipid Metabolism
- Immunology
Background:
- Coronary artery disease (CAD) is a leading cause of mortality globally.
- Low-density lipoprotein (LDL) cholesterol is a key risk factor for atherosclerosis.
- The role of LDL metabolism in immune cells in CAD pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate LDL degradation rates in peripheral blood mononuclear leukocytes (MNL) from patients with and without CAD.
- To determine if altered LDL composition in CAD patients affects LDL degradation.
- To explore the relationship between LDL metabolism in MNL and CAD.
Main Methods:
- Isolation of LDL and MNL from CAD patients (n=11) and controls (n=11).
- In vitro assessment of LDL degradation rates in MNL using autologous and homologous LDL.
- Analysis of LDL composition, including apo B and cholesteryl ester content.
Main Results:
- CAD-MNL showed a 1.7-fold higher rate of LDL degradation compared to control-MNL (P<0.05).
- Increased LDL degradation was attributed to enhanced receptor-mediated uptake in CAD-MNL.
- LDL from CAD patients had altered composition, with a higher apo B to cholesteryl ester ratio and 14.8% less cholesteryl ester (P<0.01).
Conclusions:
- CAD patients, even with normal LDL cholesterol, display increased LDL catabolism and altered LDL particle composition.
- These metabolic abnormalities, including increased LDL influx into MNL, may contribute to coronary heart disease development.
- Further research into these mechanisms could reveal novel therapeutic targets for CAD.
Abstract:
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.