Lang Maria G, Vinagre Carmen Gc, Bonfa Eloisa, Freitas Fatima R, Pasoto Sandra G, Brito Tatiane S, Seguro Luciana Pc, Maranhão Raul C, Borba Eduardo F
Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, 42523Universidade de Sao Paulo, Sao Paulo, Brazil.
Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, 42523Universidade de Sao Paulo, Sao Paulo, Brazil.
Lupus. 2022 May;31(6):659-665. doi: 10.1177/09612033221090127. Epub 2022 Mar 25.
The beneficial effect of hydroxychloroquine (HCQ) in decreasing LDL levels on Systemic Lupus Erythematosus (SLE) is well defined. The influence of this drug on HDL levels is still under debate and information about its effect on cholesterol reverse transport is lacking.
To evaluate the effects of HCQ on HDL levels and the transfer of lipids to this lipoprotein in SLE.
Nineteen SLE patients using only HCQ (SLE WITH HCQ), 19 SLE patients without any therapy (SLE WITHOUT THERAPY), and 19 healthy controls (CONTROL) were included. All three groups were premenopausal women age- and gender-matched. Serum lipids and apolipoproteins were determined by commercial kits. An transfer of four lipids (C-Phospolipid, H-Cholesteryl ester, H-Triglyceride, and C-Unesterified cholesterol) from a radioactively labeled nanoemulsion donor to HDL was performed in all participants.
Groups had comparable mean age, weight, height, BMI(body mass index), and waist circumference ( > .05). Mean HDL levels were higher in SLE WITH HCQ group compared to SLE WITHOUT THERAPY(58.37 ± 14.04 vs 49.79 ± 8.0 mg/dL; < .05) but lower than CONTROL (58.37 ± 14.04 vs 68.58 ± 9.99 mg/dL; < .05). Total cholesterol (TC) and LDL levels were also significantly lower in SLE WITH HCQ compared SLE WITHOUT THERAPY(148.16 ± 16.43 vs 167.11 ± 30.18 mg/dL; < .05, 75.05 ± 22.52 vs 96.05 ± 25.63 mg/dL; < .05) and CONTROL (148.16 ± 16.43 vs 174.11 ± 23.70 mg/dL; < .05, 75.05 ± 22.52 vs 88.53 ± 20.24 mg/dL; < .05). The lipid transfer to HDL study revealed a significant difference among the three groups ( = .002) with a higher transfer of unesterified cholesterol(UC) in SLE WITH HCQ compared to SLE WITHOUT THERAPY(5.40 ± 1.05% vs. 4.44 ± 1.05%; < .05). The latter was significantly decreased compared to CONTROL (5.40 ± 1.05% vs. 5.99 ± 1.71%; < .05).The percentages of transfer of triacylglycerol (4.93 ± 0.69% vs. 4.50 ± 0.69% vs. 5.14 ± 1.01%; = .054), esterified cholesterol (5.24 ± 0.70% vs. 4.96 ± 0.89% vs. 5.69 ± 1.27%; = .079), and phospholipid (15.67 ± 1.03% vs. 15.34 ± 1.44% vs. 16.47 ± 1.89%; = .066) were similar among groups.
The present study is the first to demonstrate that HCQ promoted a higher transfer of unesterified cholesterol which may account for the increased HDL levels in lupus patients under HCQ. This desirable effect may underlie the reported reduced atherosclerosis in SLE.
羟氯喹（HCQ）降低系统性红斑狼疮（SLE）患者低密度脂蛋白（LDL）水平的有益作用已得到明确证实。该药物对高密度脂蛋白（HDL）水平的影响仍存在争议，且缺乏其对胆固醇逆向转运作用的相关信息。
评估HCQ对SLE患者HDL水平以及脂质向该脂蛋白转运的影响。
纳入19例仅使用HCQ的SLE患者（HCQ治疗的SLE患者）、19例未接受任何治疗的SLE患者（未治疗的SLE患者）和19名健康对照者（对照组）。所有三组均为绝经前女性，年龄和性别匹配。使用商用试剂盒测定血清脂质和载脂蛋白。对所有参与者进行了四种脂质（C-磷脂、H-胆固醇酯、H-甘油三酯和C-未酯化胆固醇）从放射性标记的纳米乳剂供体向HDL的转运。
三组的平均年龄、体重、身高、体重指数（BMI）和腰围具有可比性（P>0.05）。与未治疗的SLE患者相比，HCQ治疗的SLE患者组的平均HDL水平更高（58.37±14.04 vs 49.79±8.0mg/dL；P<0.05），但低于对照组（58.37±14.04 vs 68.58±9.99mg/dL；P<0.05）。与未治疗的SLE患者相比，HCQ治疗的SLE患者的总胆固醇（TC）和LDL水平也显著降低（148.16±16.43 vs 167.11±30.18mg/dL；P<0.05，75.05±22.52 vs 96.05±25.63mg/dL；P<0.05），且低于对照组（148.16±16.43 vs 174.11±23.70mg/dL；P<0.05，75.05±22.52 vs 88.53±20.24mg/dL；P<0.05）。脂质向HDL的转运研究显示三组之间存在显著差异（P = 0.002），与未治疗的SLE患者相比，HCQ治疗的SLE患者中未酯化胆固醇（UC）的转运更高（5.40±1.05% vs. 4.44±1.05%；P<0.05）。与对照组相比，后者显著降低（5.40±1.05% vs. 5.99±1.71%；P<0.05）。三组之间甘油三酯（4.93±0.69% vs. 4.50±0.69% vs. 5.14±1.01%；P = 0.054）、酯化胆固醇（5.24±0.70% vs. 4.96±0.89% vs. 5.69±1.27%；P = 0.079）和磷脂（15.67±1.03% vs. 15.34±1.44% vs. 16.47±1.89%；P = 0.066）的转运百分比相似。
本研究首次证明HCQ促进了未酯化胆固醇的更高转运，这可能是HCQ治疗的狼疮患者HDL水平升高的原因。这种理想的作用可能是SLE患者动脉粥样硬化减少的基础。
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