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

Abstract

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 (14)C-cholesteryl ester ((14)C-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 (14)C-CE was significantly different in the three groups (P = 0.03). In fact, a greater FCR of (14)C-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 (14)C-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.

Effect of Medication on Microvascular Vasodilatation in Patients with Systemic Lupus Erythematosus

“…This was noted particularly in patients on steroid treatment, where antimalarial drugs lowered TG and very LDL (VLDL) in one of these studies [7] and in another study total cholesterol, VLDL and LDL levels were lower in SLE patients on the similar medical regimen [8]. Furthermore, LDL uptake from plasma is increased in SLE patients on steroids and antimalarial drugs compared with steroid-treated SLE patients, without antimalarial drugs [9].…”

“…Traditional risk factors as well as SLE-specific risk factors have been thoroughly studied and both are of importance for the development of cardiovascular disease in SLE [4][5][6]. It has been suggested that antimalarial (hydroxychloroquine and chloroquine diphosphate) treatment might improve the blood lipid profile in SLE and reduce the risk of diabetes mellitus [7][8][9][10][11].There is a clinical need for non-invasive techniques to ensure the presence of and predict the development of cardiovascular disease in SLE. Non-invasive methods have been used to investigate vessel wall changes, and revealed increased vessel wall stiffness and increased pulse wave velocity in SLE patients compared with controls [12,13].…”

“…Traditional risk factors as well as SLE-specific risk factors have been thoroughly studied and both are of importance for the development of cardiovascular disease in SLE [4][5][6]. It has been suggested that antimalarial (hydroxychloroquine and chloroquine diphosphate) treatment might improve the blood lipid profile in SLE and reduce the risk of diabetes mellitus [7][8][9][10][11].…”

Favorable effects of hydroxychloroquine on serum low density lipid in patients with systemic lupus erythematosus: A systematic review and meta‐analysis

“…36,37 six case-control studies [38][39][40][41][42][43] ) examining the effects of HCQ on LDL as shown in Figure 2a. Heterogeneity was extensive (I 2 = 94.739%).…”

Atherogenesis and Vascular Disease in SLE

“…There is no consistent data regarding whether this antithrombotic effect is present both for arterial and venous events. A beneficial effect on serum lipid levels, including patients taking corticosteroid therapy (Borba et al, 2001;Hodis et al, 1993;Sachet et al, 2007;Tam et al, 2000), was shown by a few observational studies. However, the strenght of evidence supporting a clinically meaningful beneficial effect was rated as low.…”