Characteristics of low density lipoprotein isolated from circulating immune complexes

Area of Science:

• Cardiovascular Biology
• Immunology
• Lipid Metabolism

Background:

• Circulating immune complexes (CIC) containing low-density lipoprotein (LDL) are associated with coronary atherosclerosis.
• The specific characteristics of LDL within these CICs require further investigation.

Purpose of the Study:

• To investigate the chemical composition and physical characteristics of LDL within CICs (CIC-LDL).
• To compare CIC-LDL with free circulating LDL and its subfractions (desialylated and sialylated LDL).
• To determine the atherogenic potential of CIC-LDL and its relationship with desialylated LDL.

Main Methods:

• Isolation of CIC from patient blood using affinity chromatography.
• Isolation of CIC-LDL and free LDL via ultracentrifugation.
• Fractionation of plasma LDL using lectin-chromatography (RCA120-agarose).
• Assessment of cholesterol content in cultured aortic cells exposed to different LDL types.
• Analysis of sialic acid, lipid, oxysterol content, particle density, size, and electrophoretic mobility.

Main Results:

• CIC-LDL and desialylated LDL significantly increased intracellular cholesterol in aortic cells.
• CIC-LDL exhibited lower sialic acid levels and reduced neutral lipid/phospholipid content compared to native LDL.
• CIC-LDL particles were denser and smaller than native or desialylated LDL, with higher electrophoretic mobility.
• CIC-LDL showed elevated oxysterol content, similar to desialylated LDL.
• CIC-LDL levels correlated with plasma desialylated LDL, not total LDL.

Conclusions:

• LDL within circulating immune complexes is a multiple-modified lipoprotein resembling desialylated LDL.
• Desialylated LDL appears to be the primary component interacting with antibodies to form immune complexes.
• Multiple-modified desialylated LDL is suggested to be the circulating autoantigen in anti-LDL autoantibody-mediated atherosclerosis.