The effect of hydroxychloroquine on cholesterol synthesis depends on the profile of cholesterol metabolism. A controlled clinical study.

Autor:	Simonen P; Heart and Lung Center, Cardiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Ulander L; Heart and Lung Center, Cardiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Eklund KK; Department of Rheumatology, Helsinki University Hospital, Helsinki University, ORTON Orthopaedic Hospital of the Orton Foundation, Helsinki, Finland., Niemi M; Department of Clinical Pharmacology and Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Finland.; Department of Clinical Pharmacology HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland., Backman JT; Department of Clinical Pharmacology and Individualized Drug Therapy Research Program, Faculty of Medicine, University of Helsinki, Finland.; Department of Clinical Pharmacology HUS Diagnostic Center, Helsinki University Hospital, Helsinki, Finland., Gylling H; Heart and Lung Center, Cardiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Sinisalo J; Heart and Lung Center, Cardiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Jazyk:	angličtina
Zdroj:	Atherosclerosis plus [Atheroscler Plus] 2024 Mar 01; Vol. 55, pp. 93-97. Date of Electronic Publication: 2024 Mar 01 (Print Publication: 2024).
DOI:	10.1016/j.athplu.2024.02.002
Abstrakt:	Background and Aims: Hydroxychloroquine (HCQ) has a variable effect on cholesterol synthesis. To clarify this, we assessed the effect of HCQ on the cholesterol-synthesis pathway in individuals with low and high cholesterol absorption efficiency. Method: A total of 53 acute myocardial infarction patients with a constant statin dose randomized to receive HCQ or placebo for six months in a double-blind manner, were classified further into low (n = 26) and high (n = 27) cholesterol absorbers based on the median baseline serum cholestanol level. Serum lipids and biomarkers of cholesterol synthesis (squalene, lanosterol, zymostenol, desmosterol, and lathosterol) and absorption efficiency (sitosterol and cholestanol), were measured at baseline and one-, six-, and 12-month follow-up visits. Results: In low cholesterol absorbers, serum cholesterol concentration and cholesterol synthesis and absorption biomarkers did not differ between the HCQ and placebo groups. At one month, high cholesterol absorbers with HCQ had lower serum cholesterol concentration and serum lanosterol to cholesterol ratio in comparison to the placebo group (HCQ 3.18 ± 0.62 vs. placebo 3.71 ± 0.65, p = 0.042, and HCQ 10.4 ± 2.55 vs. placebo 13.1 ± 2.36, p = 0.008, respectively). At 12 months, serum desmosterol to cholesterol ratio was lower in HCQ users (HCQ 47.1 ± 7.08 vs. placebo 59.0 ± 13.1, p = 0.011). Conclusions: HCQ affects the cholesterol-synthesis pathway in high cholesterol absorbers. It reduces serum lanosterol and desmosterol ratios and consequently serum cholesterol concentration possibly by inhibiting the activity of lanosterol synthase as described earlier in vitro studies. Trial Registration: ClinicalTrials.gov Identifier: NCT02648464. (© 2024 The Authors.)
Databáze:	MEDLINE
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