Related Experiment Videos
Characteristics of low-density lipoprotein subfractions from patients with coronary artery disease
O Jaakkola1, T Solakivi, V V Tertov
1Department of Biomedical Sciences, University of Tampere, Finland.
Insights
Dense low-density lipoprotein (LDL) from coronary artery disease (CAD) patients promotes cholesterol buildup in cells. This atherogenicity is linked to lower sialic acid content in these denser LDL particles.
Area of Science:
- Cardiovascular Science
- Lipid Metabolism
- Atherosclerosis Research
Background:
- Low-density lipoprotein (LDL) from coronary artery disease (CAD) patients enhances cholesterol ester accumulation in aortic cells.
- LDL in CAD patients exhibits higher mean density, suggesting altered subspecies distribution and potential atherogenicity.
- Investigating LDL subfractions' properties and effects on cellular lipid metabolism is crucial for understanding CAD.
Purpose of the Study:
- To isolate and characterize LDL subfractions from CAD patients and healthy controls.
- To determine the effects of isolated LDL subfractions on lipid metabolism and cholesterol accumulation in arterial cells and macrophages.
- To elucidate the relationship between LDL subspecies, sialic acid content, and atherogenicity.
Main Methods:
- LDL was isolated and fractionated into five subfractions (by density) from plasma pools of CAD patients and controls using gradient ultracentrifugation.
- Analyzed LDL subfractions for particle diameter, chemical composition, and sialic acid content.
- Assessed the impact of LDL subfractions on lipid content and cholesterol esterification in cultured human aortic intimal cells and mouse peritoneal macrophages.
Main Results:
- No significant differences in chemical composition of LDL subfractions between CAD patients and controls were found.
- Dense LDL subfractions, particularly from CAD patients, showed reduced sialic acid content.
- LDL subfractions with lower sialic acid content promoted cholesterol ester incorporation in macrophages and increased cholesterol ester content in aortic cells.
Conclusions:
- Dense LDL subfractions from CAD patients are atherogenic, promoting intracellular cholesterol ester accumulation.
- Reduced sialic acid content in LDL subspecies is associated with increased atherogenicity.
- These findings highlight a potential mechanism linking specific LDL characteristics to CAD progression.
Background:
The low-density lipoprotein (LDL) of patients with coronary artery disease (CAD) has been reported to enhance cholesterol ester accumulation in aortic cells. The LDL of patients with CAD also has a higher mean density than the LDL of healthy subjects, indicating a different subspecies distribution. Because these density differences may be associated with altered metabolism and atherogenicity of LDL, we studied the properties and effects of isolated LDL subfractions on cell lipid metabolism and cholesterol accumulation.
Methods:
Plasma pools of patients with angiographically proven CAD (A) and healthy controls (C) were used to isolate and fractionate LDL into five subfractions (1 to 5, from the lowest to the highest density) by gradient ultracentrifugation. Each of the LDL subfractions was analyzed for particle diameter, chemical composition, sialic acid content, and their effect on lipid content and cholesterol esterification in arterial cell and macrophage cultures, respectively.
Results:
The chemical compositions of the respective subfractions revealed no differences between patients and controls, except that the sialic acid content was reduced in dense LDL subfractions, especially in the samples from patients with CAD (fractions A3, A4, A5, and C5). LDL subfractions with reduced sialic acid content also enhanced the incorporation of [14C]-oleate into cholesterol esters in mouse peritoneal macrophage cultures (fractions A4, A5, and C5) and increased the cholesterol ester content in primary cultures of human aortic intimal cells (fractions A3, A4, A5, and C5).
Conclusions:
The results suggest that the dense LDL subfractions of patients with CAD are atherogenic by promoting intracellular cholesterol ester accumulation. The results also suggest that the atherogenicity is associated with reduced sialic acid content of the LDL subspecies.