{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:11:55Z","timestamp":1791555115621,"version":"4.3.4"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Transthyretin amyloid cardiomyopathy (ATTR-CM) causes a restrictive cardiomyopathy resulting in heart failure (HF). Signaling pathways associated with ATTR-CM are not well defined. The purpose of this study was to identify signaling pathways that are dysregulated in ATTR-CM compared with controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      This was a case-control study of cases with ATTR-CM, internal controls with hypertensive left ventricular hypertrophy, and external controls with HF. For model development, ATTR-CM cases were age- and sex-matched with internal controls with hypertensive left ventricular hypertrophy. Plasma proteomics profiling of 7289 proteins was conducted. A sparse partial least squares discriminant analysis was performed to develop a proteomics-based discrimination model from 70% of the data (ie, the training set), and the discriminative ability was tested in the remaining 30% of the data (ie, the internal test set). External validation using HF controls was also conducted. Pathway analysis of significantly (ie, univariable\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;10\n                      <jats:sup>\u22126<\/jats:sup>\n                      ) dysregulated proteins was executed. Signaling pathways with a false discovery rate &lt;0.05 were declared positive.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>The analysis included 169 cases and 220 controls. A total of 211 discriminant proteins were identified in the training set from the proteomics-based model developed to distinguish ATTR-CM cases from 170 internal controls with hypertensive left ventricular hypertrophy. The area under the receiver-operating characteristic curve to discriminate ATTR-CM in the test set from 50 external controls with HF was 0.89 (95% CI, 0.82\u20130.96). The sensitivity was 0.90 (95% CI, 0.75\u20130.97), and the specificity was 0.86 (95% CI, 0.72\u20130.96). Pathway analysis revealed the PI3K-Akt (phosphoinositide-3-kinase-protein kinase) pathway and its related pathways (eg, JAK-STAT [Janus kinase-signal transducer and activator of transcription]) were dysregulated. Dysregulation of previously identified pathways, such as the complement and coagulation cascade pathways, was also observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>This study reveals a distinct proteomic profile of ATTR-CM compared with controls with HF, and elucidates both novel and known signaling pathways that are differentially regulated in ATTR-CM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.125.013220","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T16:01:21Z","timestamp":1769097681000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Proteomics Profiling Reveals Circulating Biomarkers and Dysregulated Pathways in Transthyretin Amyloid Cardiomyopathy"],"prefix":"10.1161","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7082-8237","authenticated-orcid":true,"given":"Ree","family":"Lu","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine (R.L., A.N., K.A., M.S.M., Y.J.S.), Columbia University Irving Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5615-7328","authenticated-orcid":true,"given":"Ani","family":"Nalbandian","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine (R.L., A.N., K.A., M.S.M., Y.J.S.), Columbia University Irving Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5395-1887","authenticated-orcid":true,"given":"Keitaro","family":"Akita","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine (R.L., A.N., K.A., M.S.M., Y.J.S.), Columbia University Irving Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4653-9330","authenticated-orcid":true,"given":"Sergio","family":"Teruya","sequence":"additional","affiliation":[{"name":"Clinical Cardiovascular Research Laboratory for the Elderly (S.T., D.B., A.M.S., M.S.M.), Columbia University Irving Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Bampatsias","sequence":"additional","affiliation":[{"name":"Clinical Cardiovascular Research Laboratory for the Elderly (S.T., D.B., A.M.S., M.S.M.), Columbia University Irving Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4498-2396","authenticated-orcid":true,"given":"Alfonsina Mirabal","family":"Santos","sequence":"additional","affiliation":[{"name":"Clinical Cardiovascular Research Laboratory for the Elderly (S.T., D.B., A.M.S., M.S.M.), Columbia University Irving Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5400-5008","authenticated-orcid":true,"given":"Mathew S.","family":"Maurer","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine (R.L., A.N., K.A., M.S.M., Y.J.S.), Columbia University Irving Medical Center, New York, NY."},{"name":"Clinical Cardiovascular Research Laboratory for the Elderly (S.T., D.B., A.M.S., M.S.M.), Columbia University Irving Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3494-307X","authenticated-orcid":true,"given":"Yuichi J.","family":"Shimada","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine (R.L., A.N., K.A., M.S.M., Y.J.S.), Columbia University Irving Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2013.11.004"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.0442"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2021.3070"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000792"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1805689"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2305434"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.016567"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-019-09896-z"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1507719112"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1080\/14789450.2023.2195096"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.6b00998"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaccao.2020.08.013"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3109\/13506129.2012.674989"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026332"},{"key":"e_1_3_3_16_2","first-page":"S5","article-title":"SOMAmers and SOMAscan - a protein biomarker discovery platform for rapid analysis of sample collections from bench top to the clinic.","volume":"24","author":"Hensley P","year":"2013","unstructured":"Hensley P. SOMAmers and SOMAscan - a protein biomarker discovery platform for rapid analysis of sample collections from bench top to the clinic. J Biomol Tech. 2013;24(Suppl):S5.","journal-title":"J Biomol Tech"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbx124"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-253"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw937"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaccao.2020.06.007"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx589"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.06.033"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.020358"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1177\/03000605211031433"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1336102"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep42532"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-44680-3"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti448"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13258"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.7326\/M23-2328"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2413445"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.11.022"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/ehjci\/jev014"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17033-7"}],"container-title":["Circulation: Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCHEARTFAILURE.125.013220","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T15:36:19Z","timestamp":1773243379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCHEARTFAILURE.125.013220"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":33,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1161\/CIRCHEARTFAILURE.125.013220"],"URL":"https:\/\/doi.org\/10.1161\/circheartfailure.125.013220","relation":{},"ISSN":["1941-3289","1941-3297"],"issn-type":[{"value":"1941-3289","type":"print"},{"value":"1941-3297","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-04-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}