Decreased transcription, expression and function of low-density lipoprotein receptor in leukocytes from patients with...

Area of Science:

• Immunology
• Cardiovascular Medicine
• Metabolic Disorders

Background:

• Systemic lupus erythematosus (SLE) is associated with increased cardiovascular disease risk.
• Impaired low-density lipoprotein receptor (LDLR) function contributes to hypercholesterolemia and atherosclerosis.
• The role of LDLR in SLE pathogenesis remains incompletely understood.

Purpose of the Study:

• To investigate the transcription, expression, and function of LDLR in leukocytes of SLE patients.
• To determine the relationship between LDLR function and SLE disease activity or treatment.
• To explore potential mechanisms underlying LDLR dysfunction in SLE.

Main Methods:

• Quantification of LDLR and glyceraldehyde-3-phosphate dehydrogenase (GADPH) mRNA ratios in leukocytes.
• Assessment of LDLR protein expression.
• Measurement of LDL-DiI uptake to evaluate LDLR function.
• Analysis of plasma lipid profiles and anti-oxLDL autoantibodies (AAb).

Main Results:

• SLE patients exhibited significantly lower LDLR mRNA expression and LDL-DiI uptake compared to normal healthy donors (NHD) (p < 0.001).
• SLE patients had significantly higher total cholesterol, LDL cholesterol, and anti-oxLDL AAb levels (p < 0.0001).
• No correlation was found between LDLR status and SLE disease activity index or treatment, indicating treatment independence.

Conclusions:

• Decreased LDLR transcription, expression, and function in SLE leukocytes contribute to elevated plasma LDL cholesterol and oxLDL AAb.
• This LDLR impairment is likely mediated by sterol regulatory binding protein and increases vascular disease risk in SLE.
• The findings highlight a potential therapeutic target for managing cardiovascular complications in SLE.