Decreased transcription, expression and function of low-density lipoprotein receptor in leukocytes from patients with systemic lupus erythematosus.
The low-density lipoprotein receptor (LDLR) is directly involved in the metabolism of low-density lipoprotein (LDL) and its impairment causes accumulation of plasmatic LDL leading to atherosclerosis, a prevalent disease in patients with systemic lupus erythematosus (SLE). We studied LDLR transcription, expression and function in leukocytes patients with SLE and normal healthy donors (NHD). The ratio LDLR/glyceraldehyde-3-phosphate dehydrogenase (GADPH) mRNAs the expression of LDLR and the uptake of LDL-DiI were significantly lower (p < 0.001) in the patients with SLE. On the contrary, patients with SLE had significantly higher (p < 0.0001) levels of total cholesterol, LDL cholesterol and anti-oxLDL autoantibodies (AAb) as compared to NHD. No correlation between LDLR transcription, expression and function with the SLE disease activity index or with treatment was found. The decreased function of LDLR was independent of treatment. It seems dependent on the sterol regulatory binding protein and may be responsible for the increase of plasma LDL cholesterol and oxLDL AAb further increasing the risk of vascular diseases.
Rivas
Liliana
L
Facultad de Medicina, Instituto de Inmunología, Universidad Central de Venezuela, Caracas, Venezuela.
Zabaleta
Mercedes
M
Toro
Félix
F
Bianco
Nicolás E
NE
De Sanctis
Juan B
JB
D000328:Adult; D001323:Autoantibodies / Q000097:blood; D015152:Blotting, Northern; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011973:Receptors, LDL / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D001323:Autoantibodies; D008078:Cholesterol, LDL; D011973:Receptors, LDL; D002784:Cholesterol