{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T09:43:51Z","timestamp":1793094231764,"version":"4.5.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Hypertrophic cardiomyopathy (HCM) is caused by mutations in the genes coding for proteins essential in normal myocardial contraction. However, it remains unclear through which molecular pathways gene mutations mediate the development of HCM. The objectives were to determine plasma protein biomarkers of HCM and to reveal molecular pathways differentially regulated in HCM.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>We conducted a multicenter case-control study of cases with HCM and controls with hypertensive left ventricular hypertrophy. We performed plasma proteomics profiling of 1681 proteins. We performed a sparse partial least squares discriminant analysis to develop a proteomics-based discrimination model with data from 1 institution (ie, the training set). We tested the discriminative ability in independent samples from the other institution (ie, the test set). As an exploratory analysis, we executed pathway analysis of significantly dysregulated proteins. Pathways with false discovery rate &lt;0.05 were declared positive.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>The study included 266 cases and 167 controls (n=308 in the training set; n=125 in the test set). Using the proteomics-based model derived from the training set, the area under the receiver operating characteristic curve was 0.89 (95% CI, 0.83\u20130.94) in the test set. Pathway analysis revealed that the Ras-MAPK (mitogen-activated protein kinase) pathway, along with its upstream and downstream pathways, was upregulated in HCM. Pathways involved in inflammation and fibrosis\u2014for example, the TGF (transforming growth factor)-\u03b2 pathway\u2014were also upregulated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>This study serves as the largest-scale investigation with the most comprehensive proteomics profiling in HCM, revealing circulating biomarkers and exhibiting both novel (eg, Ras-MAPK) and known (eg, TGF-\u03b2) pathways differentially regulated in HCM.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.120.007849","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T09:00:19Z","timestamp":1625130019000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":59,"title":["Comprehensive Proteomics Profiling Reveals Circulating Biomarkers of Hypertrophic Cardiomyopathy"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3494-307X","authenticated-orcid":true,"given":"Yuichi J.","family":"Shimada","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine (Y.J.S., L.W.L., M.S.M., M.P.R.), Columbia University Irving Medical Center, New York, NY."},{"name":"Cardiology Division, Department of Medicine (Y.J.S., M.A.F.), Massachusetts General Hospital, Harvard Medical School, Boston."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5805-9369","authenticated-orcid":true,"given":"Yoshihiko","family":"Raita","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine (Y.R., K.H.), Massachusetts General Hospital, Harvard Medical School, Boston."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3931-4085","authenticated-orcid":true,"given":"Lusha 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