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 e...
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| Veröffentlicht in: | Chemistry and physics of lipids 2023-11, Vol.257, p.105348-105348, Article 105348 |
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| creator | Cerda, Alvaro Bortolin, Raul Hernandes Yoshinaga, Marcos Yukio Freitas, Renata Caroline Costa de Dagli-Hernandez, Carolina Borges, Jessica Bassani Oliveira, Victor Fernandes de Gonçalves, Rodrigo Marques Faludi, Andre Arpad Bastos, Gisele Medeiros Hirata, Rosario Dominguez Crespo Hirata, Mario Hiroyuki |
| description | 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 |
| doi_str_mv | 10.1016/j.chemphyslip.2023.105348 |
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•Statins change serum lipidomic profile in Familial Hypercholesterolemia patients.•Posphatidyl-inositol and triacylglycerol are key in posttreatment discriminant analysis.•Posphatidyl-inositol molecules are predictive biomarkers of statin response.</description><identifier>ISSN: 0009-3084</identifier><identifier>EISSN: 1873-2941</identifier><identifier>DOI: 10.1016/j.chemphyslip.2023.105348</identifier><identifier>PMID: 37827478</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Adult ; adults ; atherosclerosis ; atorvastatin ; Biomarkers ; biosynthesis ; blood lipids ; blood serum ; Cholesterol ; Cholesterol, LDL ; electrospray ionization mass spectrometry ; Familial hypercholesterolemia ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use ; hypercholesterolemia ; Hyperlipoproteinemia Type II - drug therapy ; lipid composition ; lipid metabolism ; Lipid-lowering drugs ; Lipidomics ; low density lipoprotein cholesterol ; Phosphatidyl-inositol ; phosphatidylinositols ; physics ; risk ; Statin ; triacylglycerols ; ultra-performance liquid chromatography</subject><ispartof>Chemistry and physics of lipids, 2023-11, Vol.257, p.105348-105348, Article 105348</ispartof><rights>2023 Elsevier B.V.</rights><rights>Copyright © 2023 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c354t-66667c22bebfdf2814423f73cc5c9c54b1d7d86181a761fa520dce7b97d52aa83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.chemphyslip.2023.105348$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,778,782,3539,27911,27912,45982</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37827478$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cerda, Alvaro</creatorcontrib><creatorcontrib>Bortolin, Raul Hernandes</creatorcontrib><creatorcontrib>Yoshinaga, Marcos Yukio</creatorcontrib><creatorcontrib>Freitas, Renata Caroline Costa de</creatorcontrib><creatorcontrib>Dagli-Hernandez, Carolina</creatorcontrib><creatorcontrib>Borges, Jessica Bassani</creatorcontrib><creatorcontrib>Oliveira, Victor Fernandes de</creatorcontrib><creatorcontrib>Gonçalves, Rodrigo Marques</creatorcontrib><creatorcontrib>Faludi, Andre Arpad</creatorcontrib><creatorcontrib>Bastos, Gisele Medeiros</creatorcontrib><creatorcontrib>Hirata, Rosario Dominguez Crespo</creatorcontrib><creatorcontrib>Hirata, Mario Hiroyuki</creatorcontrib><title>Lipidomic analysis identified potential predictive biomarkers of statin response in subjects with Familial hypercholesterolemia</title><title>Chemistry and physics of lipids</title><addtitle>Chem Phys Lipids</addtitle><description>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.
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•Statins change serum lipidomic profile in Familial Hypercholesterolemia patients.•Posphatidyl-inositol and triacylglycerol are key in posttreatment discriminant analysis.•Posphatidyl-inositol molecules are predictive biomarkers of statin response.</description><subject>Adult</subject><subject>adults</subject><subject>atherosclerosis</subject><subject>atorvastatin</subject><subject>Biomarkers</subject><subject>biosynthesis</subject><subject>blood lipids</subject><subject>blood serum</subject><subject>Cholesterol</subject><subject>Cholesterol, LDL</subject><subject>electrospray ionization mass spectrometry</subject><subject>Familial hypercholesterolemia</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</subject><subject>hypercholesterolemia</subject><subject>Hyperlipoproteinemia Type II - drug therapy</subject><subject>lipid composition</subject><subject>lipid metabolism</subject><subject>Lipid-lowering drugs</subject><subject>Lipidomics</subject><subject>low density lipoprotein cholesterol</subject><subject>Phosphatidyl-inositol</subject><subject>phosphatidylinositols</subject><subject>physics</subject><subject>risk</subject><subject>Statin</subject><subject>triacylglycerols</subject><subject>ultra-performance liquid chromatography</subject><issn>0009-3084</issn><issn>1873-2941</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQhi1ERZe2fwGZG5cs_ojXzhGtKCCtxIWeLceeKLMkcbCzRXvir9fRFsQN5jLj0Tsz1vsQ8pazLWd89_649T2Mc3_OA85bwYQsfSVr84JsuNGyEk3NX5INY6ypJDP1NXmd87E8mVL8FbmW2ghda7Mhvw44Y4gjeuomN5wzZooBpgU7hEDnuKy1G-icIKBf8BFoi3F06TukTGNH8-IWnGiCPMcpAy11PrVH8EumP3Hp6b0bcVhX9OcZku_jAHmBVNKI7pZcdW7IcPecb8jD_cdv-8_V4eunL_sPh8pLVS_VroT2QrTQdqEThte1kJ2W3ivfeFW3POhgdtxwp3e8c0qw4EG3jQ5KOGfkDXl32Tun-ONUPmBHzB6GwU0QT9lKrmqujRH8n1JhtJaNZGqVNhepTzHnBJ2dExZvzpYzu6KyR_sXKruishdUZfbN85lTO0L4M_mbTRHsLwIovjwiJJs9wuQLh1TctSHif5x5Aq3Jrt0</recordid><startdate>202311</startdate><enddate>202311</enddate><creator>Cerda, Alvaro</creator><creator>Bortolin, Raul Hernandes</creator><creator>Yoshinaga, Marcos Yukio</creator><creator>Freitas, Renata Caroline Costa de</creator><creator>Dagli-Hernandez, Carolina</creator><creator>Borges, Jessica Bassani</creator><creator>Oliveira, Victor Fernandes de</creator><creator>Gonçalves, Rodrigo Marques</creator><creator>Faludi, Andre Arpad</creator><creator>Bastos, Gisele Medeiros</creator><creator>Hirata, Rosario Dominguez Crespo</creator><creator>Hirata, Mario Hiroyuki</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope></search><sort><creationdate>202311</creationdate><title>Lipidomic analysis identified potential predictive biomarkers of statin response in subjects with Familial hypercholesterolemia</title><author>Cerda, Alvaro ; Bortolin, Raul Hernandes ; Yoshinaga, Marcos Yukio ; Freitas, Renata Caroline Costa de ; Dagli-Hernandez, Carolina ; Borges, Jessica Bassani ; Oliveira, Victor Fernandes de ; Gonçalves, Rodrigo Marques ; Faludi, Andre Arpad ; Bastos, Gisele Medeiros ; Hirata, Rosario Dominguez Crespo ; Hirata, Mario Hiroyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c354t-66667c22bebfdf2814423f73cc5c9c54b1d7d86181a761fa520dce7b97d52aa83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Adult</topic><topic>adults</topic><topic>atherosclerosis</topic><topic>atorvastatin</topic><topic>Biomarkers</topic><topic>biosynthesis</topic><topic>blood lipids</topic><topic>blood serum</topic><topic>Cholesterol</topic><topic>Cholesterol, LDL</topic><topic>electrospray ionization mass spectrometry</topic><topic>Familial hypercholesterolemia</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</topic><topic>hypercholesterolemia</topic><topic>Hyperlipoproteinemia Type II - drug therapy</topic><topic>lipid composition</topic><topic>lipid metabolism</topic><topic>Lipid-lowering drugs</topic><topic>Lipidomics</topic><topic>low density lipoprotein cholesterol</topic><topic>Phosphatidyl-inositol</topic><topic>phosphatidylinositols</topic><topic>physics</topic><topic>risk</topic><topic>Statin</topic><topic>triacylglycerols</topic><topic>ultra-performance liquid chromatography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cerda, Alvaro</creatorcontrib><creatorcontrib>Bortolin, Raul Hernandes</creatorcontrib><creatorcontrib>Yoshinaga, Marcos Yukio</creatorcontrib><creatorcontrib>Freitas, Renata Caroline Costa de</creatorcontrib><creatorcontrib>Dagli-Hernandez, Carolina</creatorcontrib><creatorcontrib>Borges, Jessica Bassani</creatorcontrib><creatorcontrib>Oliveira, Victor Fernandes de</creatorcontrib><creatorcontrib>Gonçalves, Rodrigo Marques</creatorcontrib><creatorcontrib>Faludi, Andre Arpad</creatorcontrib><creatorcontrib>Bastos, Gisele Medeiros</creatorcontrib><creatorcontrib>Hirata, Rosario Dominguez Crespo</creatorcontrib><creatorcontrib>Hirata, Mario Hiroyuki</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Chemistry and physics of lipids</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cerda, Alvaro</au><au>Bortolin, Raul Hernandes</au><au>Yoshinaga, Marcos Yukio</au><au>Freitas, Renata Caroline Costa de</au><au>Dagli-Hernandez, Carolina</au><au>Borges, Jessica Bassani</au><au>Oliveira, Victor Fernandes de</au><au>Gonçalves, Rodrigo Marques</au><au>Faludi, Andre Arpad</au><au>Bastos, Gisele Medeiros</au><au>Hirata, Rosario Dominguez Crespo</au><au>Hirata, Mario Hiroyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lipidomic analysis identified potential predictive biomarkers of statin response in subjects with Familial hypercholesterolemia</atitle><jtitle>Chemistry and physics of lipids</jtitle><addtitle>Chem Phys Lipids</addtitle><date>2023-11</date><risdate>2023</risdate><volume>257</volume><spage>105348</spage><epage>105348</epage><pages>105348-105348</pages><artnum>105348</artnum><issn>0009-3084</issn><eissn>1873-2941</eissn><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 (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.
[Display omitted]
•Statins change serum lipidomic profile in Familial Hypercholesterolemia patients.•Posphatidyl-inositol and triacylglycerol are key in posttreatment discriminant analysis.•Posphatidyl-inositol molecules are predictive biomarkers of statin response.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>37827478</pmid><doi>10.1016/j.chemphyslip.2023.105348</doi><tpages>1</tpages></addata></record> |
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| subjects | Adult adults atherosclerosis atorvastatin Biomarkers biosynthesis blood lipids blood serum Cholesterol Cholesterol, LDL electrospray ionization mass spectrometry Familial hypercholesterolemia Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use hypercholesterolemia Hyperlipoproteinemia Type II - drug therapy lipid composition lipid metabolism Lipid-lowering drugs Lipidomics low density lipoprotein cholesterol Phosphatidyl-inositol phosphatidylinositols physics risk Statin triacylglycerols ultra-performance liquid chromatography |
| title | Lipidomic analysis identified potential predictive biomarkers of statin response in subjects with Familial hypercholesterolemia |
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