A cytotoxic electronegative LDL subfraction is present in human plasma

Area of Science:

• Lipid Metabolism
• Cardiovascular Biology
• Atherosclerosis Research

Background:

• Low-density lipoprotein (LDL) plays a central role in lipid transport and cardiovascular disease.
• Heterogeneity within LDL particles may influence their atherogenic potential.
• Understanding LDL subfractions is crucial for elucidating mechanisms of atherosclerosis.

Purpose of the Study:

• To isolate and characterize a minor electronegative LDL subfraction (LDL(-)) from human plasma.
• To compare the biochemical and functional properties of LDL(-) with the major LDL subfraction (LDL(+)).
• To investigate the relationship between LDL(-) levels and established risk factors for atherosclerosis.

Main Methods:

• Fast protein liquid chromatography and immunoaffinity chromatography were used for LDL subfraction isolation.
• Biochemical assays were performed to analyze lipid and protein content, oxidative markers, and receptor binding.
• Cytotoxicity assays (lactate dehydrogenase, neutral red uptake) were conducted on cultured human umbilical vein endothelial cells.
• Correlation analysis was used to assess the relationship between LDL(-) levels and clinical parameters in a cohort of subjects.

Main Results:

• A distinct electronegative LDL subfraction, LDL(-), was isolated, comprising approximately 6.7% of total LDL.
• LDL(-) exhibited increased content of sialic acid, apo C-III, and apo E compared to LDL(+).
• LDL(-) demonstrated enhanced cytotoxic effects on endothelial cells and showed a slight increase in LDL receptor binding.
• The prevalence of LDL(-) positively correlated with age, total cholesterol, and LDL cholesterol levels.

Conclusions:

• LDL(-) is a native, electronegative LDL subfraction found in human plasma.
• This subfraction possesses cytotoxic properties towards endothelial cells.
• LDL(-) is associated with key atherosclerotic risk factors and may contribute to atherogenesis through vascular endothelium alteration.