{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:26:01Z","timestamp":1788373561415,"version":"build-2803163510"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>The metabolic alterations occurring within the arterial architecture during atherosclerosis development remain poorly understood, let alone those particular to each arterial tunica. We aimed first to identify, in a spatially resolved manner, the specific metabolic changes in plaque, media, adventitia, and cardiac tissue between control and atherosclerotic murine aortas. Second, we assessed their translatability to human tissue and plasma for cardiovascular risk estimation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>In this observational study, mass spectrometry imaging (MSI) was applied to identify region-specific metabolic differences between atherosclerotic (n=11) and control (n=11) aortas from low-density lipoprotein receptor\u2013deficient mice, via histology-guided virtual microdissection. Early and advanced plaques were compared within the same atherosclerotic animals. Progression metabolites were further analyzed by MSI in 9 human atherosclerotic carotids and by targeted mass spectrometry in human plasma from subjects with elective coronary artery bypass grafting (cardiovascular risk group, n=27) and a control group (n=27).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              MSI identified 362 local metabolic alterations in atherosclerotic mice (log2 fold-change \u22651.5;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              \u22640.05). The lipid composition of cardiac tissue is altered during atherosclerosis development and presents a generalized accumulation of glycerophospholipids, except for lysolipids. Lysolipids (among other glycerophospholipids) were found at elevated levels in all 3 arterial layers of atherosclerotic aortas. LPC(18:0) (lysophosphatidylcholine;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.024) and LPA(18:1) (lysophosphatidic acid;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.025) were found to be significantly elevated in advanced plaques as compared with mouse-matched early plaques. Higher levels of both lipid species were also observed in fibrosis-rich areas of advanced- versus early-stage human samples. They were found to be significantly reduced in human plasma from subjects with elective coronary artery bypass grafting (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001 and\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.031, respectively), with LPC(18:0) showing significant association with cardiovascular risk (odds ratio, 0.479 [95% CI, 0.225\u20130.883];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.032) and diagnostic potential (area under the curve, 0.778 [95% CI, 0.638\u20130.917]).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>An altered phospholipid metabolism occurs in atherosclerosis, affecting both the aorta and the adjacent heart tissue. Plaque-progression lipids LPC(18:0) and LPA(18:1), as identified by MSI on tissue, reflect cardiovascular risk in human plasma.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.123.320278","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T10:07:00Z","timestamp":1706782020000},"page":"741-754","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Spatial Metabolomics Identifies LPC(18:0) and LPA(18:1) in Advanced Atheroma With Translation to Plasma for Cardiovascular Risk Estimation"],"prefix":"10.1161","volume":"44","author":[{"given":"Jianhua","family":"Cao","sequence":"first","affiliation":[{"name":"Maastricht MultiModal Molecular Imaging institute, M4i, Maastricht University, the Netherlands (J.C., B.S.R.C., R.M.A.H., B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0950-3558","authenticated-orcid":true,"given":"Marta","family":"Martin-Lorenzo","sequence":"additional","affiliation":[{"name":"Immunology Department, IIS-Fundaci\u00f3n Jim\u00e9nez D\u00edaz-UAM, Madrid, Spain (M.M.-L., G.A.-L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8880-9039","authenticated-orcid":true,"given":"Kim","family":"van Kuijk","sequence":"additional","affiliation":[{"name":"Department of Pathology, CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, the Netherlands (K.v.K., E.B.W., M.J.G., P.G., J.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0467-3435","authenticated-orcid":true,"given":"Elias B.","family":"Wieland","sequence":"additional","affiliation":[{"name":"Department of Pathology, CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, the Netherlands (K.v.K., E.B.W., M.J.G., P.G., J.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4906-0384","authenticated-orcid":true,"given":"Marion J.","family":"Gijbels","sequence":"additional","affiliation":[{"name":"Department of Pathology, CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, the Netherlands (K.v.K., E.B.W., M.J.G., P.G., J.C.S.)."},{"name":"Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam UMC, the Netherlands (M.J.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3177-6330","authenticated-orcid":true,"given":"Britt S.R.","family":"Claes","sequence":"additional","affiliation":[{"name":"Maastricht MultiModal Molecular Imaging institute, M4i, Maastricht University, the Netherlands (J.C., B.S.R.C., R.M.A.H., B.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeles","family":"Heredero","sequence":"additional","affiliation":[{"name":"Cardiac Surgery Service, Fundaci\u00f3n Jim\u00e9nez D\u00edaz University Hospital-UAM, Madrid, Spain (A.H., G.A.-E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6369-448X","authenticated-orcid":true,"given":"Gonzalo","family":"Aldamiz-Echevarria","sequence":"additional","affiliation":[{"name":"Cardiac Surgery Service, Fundaci\u00f3n Jim\u00e9nez D\u00edaz University Hospital-UAM, Madrid, Spain (A.H., G.A.-E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6533-7179","authenticated-orcid":true,"given":"Ron M.A.","family":"Heeren","sequence":"additional","affiliation":[{"name":"Maastricht MultiModal Molecular Imaging institute, M4i, Maastricht University, the Netherlands (J.C., B.S.R.C., R.M.A.H., 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