Alvaro Cerda , Raul Hernandes Bortolin , Marcos Yukio Yoshinaga , Renata Caroline Costa de Freitas , Carolina Dagli-Hernandez , Jessica Bassani Borges , Victor Fernandes de Oliveira , Rodrigo Marques Gonçalves , Andre Arpad Faludi , Gisele Medeiros Bastos , Rosario Dominguez Crespo Hirata , Mario Hiroyuki Hirata
{"title":"脂质组学分析确定了家族性高胆固醇血症受试者他汀类药物反应的潜在预测生物标志物。","authors":"Alvaro Cerda , Raul Hernandes Bortolin , Marcos Yukio Yoshinaga , Renata Caroline Costa de Freitas , Carolina Dagli-Hernandez , Jessica Bassani Borges , Victor Fernandes de Oliveira , Rodrigo Marques Gonçalves , Andre Arpad Faludi , Gisele Medeiros Bastos , Rosario Dominguez Crespo Hirata , Mario Hiroyuki Hirata","doi":"10.1016/j.chemphyslip.2023.105348","DOIUrl":null,"url":null,"abstract":"<div><p><span><span>Familial hypercholesterolemia (FH) is a disorder of lipid metabolism that causes elevated low-density lipoprotein cholesterol (LDL-c) and increased premature atherosclerosis risk. </span>Statins<span><span><span> 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 </span>lipidomic<span> 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 </span></span>rosuvastatin<span><span><span> (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 </span>lipids grouped into 16 classes. Statin treatment reduced drastically 8 of 13 lipid classes, generating a characteristic lipidomic profile with a significant contribution of </span>phosphatidylinositols (PI) 16:0/18:2, 18:0/18:1 and 18:0/18:2; and </span></span></span>triacylglycerols<span> (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<span> of 0.98, 0.94 and 0.91, respectively. In conclusion, statins extensively modulate the overall serum lipid<span> composition of FH individuals and these findings suggest that phosphatidyl-inositol molecules are potential predictive biomarkers of statin response.</span></span></span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Lipidomic analysis identified potential predictive biomarkers of statin response in subjects with Familial hypercholesterolemia\",\"authors\":\"Alvaro Cerda , Raul Hernandes Bortolin , Marcos Yukio Yoshinaga , Renata Caroline Costa de Freitas , Carolina Dagli-Hernandez , Jessica Bassani Borges , Victor Fernandes de Oliveira , Rodrigo Marques Gonçalves , Andre Arpad Faludi , Gisele Medeiros Bastos , Rosario Dominguez Crespo Hirata , Mario Hiroyuki Hirata\",\"doi\":\"10.1016/j.chemphyslip.2023.105348\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span><span>Familial hypercholesterolemia (FH) is a disorder of lipid metabolism that causes elevated low-density lipoprotein cholesterol (LDL-c) and increased premature atherosclerosis risk. </span>Statins<span><span><span> 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 </span>lipidomic<span> 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 </span></span>rosuvastatin<span><span><span> (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 </span>lipids grouped into 16 classes. Statin treatment reduced drastically 8 of 13 lipid classes, generating a characteristic lipidomic profile with a significant contribution of </span>phosphatidylinositols (PI) 16:0/18:2, 18:0/18:1 and 18:0/18:2; and </span></span></span>triacylglycerols<span> (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<span> of 0.98, 0.94 and 0.91, respectively. In conclusion, statins extensively modulate the overall serum lipid<span> composition of FH individuals and these findings suggest that phosphatidyl-inositol molecules are potential predictive biomarkers of statin response.</span></span></span></p></div>\",\"PeriodicalId\":275,\"journal\":{\"name\":\"Chemistry and Physics of Lipids\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2023-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chemistry and Physics of Lipids\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0009308423000701\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemistry and Physics of Lipids","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0009308423000701","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Lipidomic analysis identified potential predictive biomarkers of statin response in subjects with Familial hypercholesterolemia
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.
期刊介绍：
Chemistry and Physics of Lipids publishes research papers and review articles on chemical and physical aspects of lipids with primary emphasis on the relationship of these properties to biological functions and to biomedical applications.
Accordingly, the journal covers: advances in synthetic and analytical lipid methodology; mass-spectrometry of lipids; chemical and physical characterisation of isolated structures; thermodynamics, phase behaviour, topology and dynamics of lipid assemblies; physicochemical studies into lipid-lipid and lipid-protein interactions in lipoproteins and in natural and model membranes; movement of lipids within, across and between membranes; intracellular lipid transfer; structure-function relationships and the nature of lipid-derived second messengers; chemical, physical and functional alterations of lipids induced by free radicals; enzymatic and non-enzymatic mechanisms of lipid peroxidation in cells, tissues, biofluids; oxidative lipidomics; and the role of lipids in the regulation of membrane-dependent biological processes.
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