Lipidomic analysis identified potential predictive biomarkers of statin response in subjects with Familial hypercholesterolemia
Chem. Phys. lipids
; 257: 105348, nov.2023. ilus
Article
in English
| CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP
| ID: biblio-1524856
Responsible library:
BR79.1
ABSTRACT
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 (4070 % reduction, n = 9) or poor (333 % 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) 160/182, 180/181 and 180/182; and triacylglycerols (TAG) 182x2/183, 181/182/183, 161/182x2, 161/182/183 and 161/182/Arachidonic acid (p-adjusted <0.05). Biomarker analysis implemented in MetaboAnalyst subsequently identified PI 161/180, 160/182 and 180/182 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.
Full text:
Available
Collection:
National databases
/
Brazil
Database:
CONASS
/
Sec. Est. Saúde SP
/
SESSP-IDPCPROD
Main subject:
Biomarkers
/
Hyperlipoproteinemia Type II
Type of study:
Prognostic study
/
Risk factors
Language:
English
Journal:
Chem. Phys. lipids
Year:
2023
Document type:
Article
Institution/Affiliation country:
Hospital Beneficiencia Portuguesa de São Paulo/BR
/
Institute of Cardiology Dante Pazzanese/BR
/
Universidad de La Frontera/CL
/
University of São Paulo/BR