Lipidomic analysis identified potential predictive biomarkers of statin response in subjects with Familial hypercholesterolemia.

Autor: Cerda A; Department of Basic Sciences, Center of Excellence in Translational Medicine, CEMT-BIOREN, Universidad de La Frontera, Temuco 4810296, Chile., Bortolin RH; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil; Department of Cardiology, Boston Children's Hospital/Harvard Medical School, Boston, MA 02115, United States., Yoshinaga MY; Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, São Paulo 05508-000, Brazil., Freitas RCC; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil; Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA 02115, United States., Dagli-Hernandez C; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil., Borges JB; Department of Research, Hospital Beneficiencia Portuguesa de Sao Paulo, Sao Paulo 01323-001, Brazil., Oliveira VF; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil., Gonçalves RM; Medical Division, Institute of Cardiology Dante Pazzanese, Sao Paulo 04012-909, Brazil., Faludi AA; Medical Division, Institute of Cardiology Dante Pazzanese, Sao Paulo 04012-909, Brazil., Bastos GM; Department of Research, Hospital Beneficiencia Portuguesa de Sao Paulo, Sao Paulo 01323-001, Brazil., Hirata RDC; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil., Hirata MH; Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil. Electronic address: mhhirata@usp.br.
Jazyk: angličtina
Zdroj: Chemistry and physics of lipids [Chem Phys Lipids] 2023 Nov; Vol. 257, pp. 105348. Date of Electronic Publication: 2023 Oct 11.
DOI: 10.1016/j.chemphyslip.2023.105348
Abstrakt: Familial hypercholesterolemia (FH) is a disorder of lipid metabolism that causes elevated low-density lipoprotein cholesterol (LDL-c) and increased premature atherosclerosis risk. Statins inhibit endogenous cholesterol biosynthesis, which reduces LDL-c plasma levels and prevent from cardiovascular events. This study aimed to explore the effects of statin treatment on serum lipidomic profile and to identify biomarkers of response in subjects with FH. Seventeen adult FH patients underwent a 6-week washout followed by 4-week treatment with atorvastatin (80 mg/day) or rosuvastatin (40 mg/day). LDL-c response was considered good (40-70 % reduction, n = 9) or poor (3-33 % reduction, n = 8). Serum lipidomic profile was analyzed by ultra-high-performance liquid chromatography combined with electrospray ionization tandem time-of-flight mass spectrometry, and data were analyzed using MetaboAnalyst v5.0. Lipidomic analysis identified 353 lipids grouped into 16 classes. Statin treatment reduced drastically 8 of 13 lipid classes, generating a characteristic lipidomic profile with a significant contribution of phosphatidylinositols (PI) 16:0/18:2, 18:0/18:1 and 18:0/18:2; and triacylglycerols (TAG) 18:2x2/18:3, 18:1/18:2/18:3, 16:1/18:2x2, 16:1/18:2/18:3 and 16:1/18:2/Arachidonic acid (p-adjusted <0.05). Biomarker analysis implemented in MetaboAnalyst subsequently identified PI 16:1/18:0, 16:0/18:2 and 18:0/18:2 as predictors of statin response with and receiver operating characteristic (ROC) areas under the curve of 0.98, 0.94 and 0.91, respectively. In conclusion, statins extensively modulate the overall serum lipid composition of FH individuals and these findings suggest that phosphatidyl-inositol molecules are potential predictive biomarkers of statin response.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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