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Hydroxychloroquine increased cholesterol transfer to high-density lipoprotein in systemic lupus erythematosus: A possible mechanism for the reversal of atherosclerosis in the disease

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Author(s):
Lang, Maria G. ; Vinagre, Carmen G. C. ; Bonfa, Eloisa ; Freitas, Fatima R. ; Pasoto, Sandra G. ; Brito, Tatiane S. ; Seguro, Luciana P. C. ; Maranhao, Raul C. ; Borba, Eduardo F.
Total Authors: 9
Document type: Journal article
Source: Lupus; v. 31, n. 6, p. 7-pg., 2022-03-25.
Abstract

Introduction 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. Objective To evaluate the effects of HCQ on HDL levels and the transfer of lipids to this lipoprotein in SLE. Methods 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 in vitro transfer of four lipids (C-14-Phospolipid, H-3-Cholesteryl ester, H-3-Triglyceride, and C-14-Unesterified cholesterol) from a radioactively labeled nanoemulsion donor to HDL was performed in all participants. Results Groups had comparable mean age, weight, height, BMI(body mass index), and waist circumference (p > .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; p < .05) but lower than CONTROL (58.37 +/- 14.04 vs 68.58 +/- 9.99 mg/dL; p < .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; p < .05, 75.05 +/- 22.52 vs 96.05 +/- 25.63 mg/dL; p < .05) and CONTROL (148.16 +/- 16.43 vs 174.11 +/- 23.70 mg/dL; p < .05, 75.05 +/- 22.52 vs 88.53 +/- 20.24 mg/dL; p < .05). The in vitro lipid transfer to HDL study revealed a significant difference among the three groups (p = .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%; p < .05). The latter was significantly decreased compared to CONTROL (5.40 +/- 1.05% vs. 5.99 +/- 1.71%; p < .05).The percentages of transfer of triacylglycerol (4.93 +/- 0.69% vs. 4.50 +/- 0.69% vs. 5.14 +/- 1.01%; p = .054), esterified cholesterol (5.24 +/- 0.70% vs. 4.96 +/- 0.89% vs. 5.69 +/- 1.27%; p = .079), and phospholipid (15.67 +/- 1.03% vs. 15.34 +/- 1.44% vs. 16.47 +/- 1.89%; p = .066) were similar among groups. Conclusion 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. (AU)

FAPESP's process: 15/03756-4 - Assessment of relevance of blood levels of drugs in the monitoring rheumatic autoimmune diseases: safety, effectiveness and adherence to therapy
Grantee:Eloisa Silva Dutra de Oliveira Bonfá
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 17/14352-7 - Assessment of relevance of blood levels of drugs in the monitoring rheumatic autoimmune diseases: safety, effectiveness and adherence to therapy
Grantee:Tatiana Do Nascimento Pedrosa
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 14/03742-0 - Nanoparticles that bind to lipoprotein receptors in the treatment atherosclerosis, acute myocardial infarction, post-heart transplantation status, cancer and endometriosis
Grantee:Raul Cavalcante Maranhao
Support Opportunities: Research Projects - Thematic Grants