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Chloroquine increases low-density lipoprotein removal from plasma in systemic lupus patients

Rheumatology Division and Lipid Metabolism Laboratory of the Heart Institute (InCor) of the Medical School Hospital and Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil

E.F. Borba

Rheumatology Division and Lipid Metabolism Laboratory of the Heart Institute (InCor) of the Medical School Hospital and Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil, reumato{at}edu.usp.br

E. Bonfá

Rheumatology Division and Lipid Metabolism Laboratory of the Heart Institute (InCor) of the Medical School Hospital and Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil

C.G.C. Vinagre

Rheumatology Division and Lipid Metabolism Laboratory of the Heart Institute (InCor) of the Medical School Hospital and Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil

V.M. Silva

Rheumatology Division and Lipid Metabolism Laboratory of the Heart Institute (InCor) of the Medical School Hospital and Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil

R.C. Maranhão

Rheumatology Division and Lipid Metabolism Laboratory of the Heart Institute (InCor) of the Medical School Hospital and Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil

Low-density lipoprotein (LDL) pathway in systemic lupus erythematosus (SLE) patients taking chloroquine diphosphate (CDP) was evaluated through the kinetic behavior of a radioactive cholesterol-rich nanoemulsion (LDE) that resembles the LDL lipidic structure. LDE was labeled with ¹⁴C-cholesteryl ester (¹⁴C-CE), then IV injected in inactive female SLE patients: 10 taking CDP (CDP), 10 without therapy (NO THERAPY); and 10 normal subjects (CONTROL). Groups were age-matched and followed rigorous selection criteria of conditions that interfere in the lipid profile. Blood samples were collected in pre-established intervals after infusion for radioactivity measurement. Fasting lipoproteins were determined in the beginning of kinetic studies. Fractional clearance rate (FCR) of ¹⁴C-CE was significantly different in the three groups (P = 0.03). In fact, a greater FCR of ¹⁴C-CE was observed in CDP compared to NO THERAPY (0.076 ± 0.037 versus 0.046 ± 0.021 h^{— 1}; P < 0.05) and to CONTROL (0.0516 ± 0.0125 h^{— 1}; P < 0.05). Accordingly, a significant lower total and LDL cholesterol were observed in CDP (156 ± 16 and 88 ± 16 mg/dl) compared to NO THERAPY (174 ± 15 and 108 ± 17 mg/dl; P < 0.05) and to CONTROL (200 ± 24 and 118 ± 23 mg/dl; P < 0.05). In contrast, no difference in (FCR) of ¹⁴C-CE of NO THERAPY and CONTROL groups was observed. This is the first in vivo demonstration that LDE removal by LDL receptor from plasma is increased in SLE patients taking CDP with a consequent beneficial decrease in LDL-c levels. Lupus (2007) 16, 273—278.

Key Words: atherosclerosis • chloroquine • dyslipoproteinemia • emulsions • lipoproteins • low-Density lipoprotein • systemic lupus erythematosus

Lupus, Vol. 16, No. 4, 273-278 (2007)
DOI: 10.1177/09612033070160040901


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