{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T08:08:59Z","timestamp":1787990939552,"version":"build-2784847793"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent and has few treatments. The molecular mechanisms and resultant signaling pathways that underlie the development of HFpEF are poorly defined. It has been proposed that activation of proinflammatory pathways plays a role in the development of cardiac fibrosis. The signature of gene expression (transcriptome) of previously validated left ventricular biopsies obtained from patients with HFpEF and matched referent controls allows for an unbiased assessment of proinflammatory and profibrotic signaling pathways and genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Epicardial left ventricular biopsies from stringently selected HFpEF patients (HFpEF, n=16) and referent control patients (CTR, n=14) were obtained during aortocoronary bypass surgery. The subepicardial myocardium was flash-frozen to build a repository that was parallel-processed for RNA sequencing to allow for an unsupervised in-depth comparison of the left ventricular transcriptome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      The average patient age was 67\u00b110 years. When compared with controls, patients with HFpEF were hypertensive with a higher body mass index (kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      : 30\u00b15 versus 37\u00b16;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.01) and elevated NT-proBNP levels (pg\/mL: 155 [89\u2013328] versus 1554 [888\u20132178];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001). The transcriptome analysis revealed differential expression of 477 genes many of which were involved in profibrotic pathways including extracellular matrix production and posttranslational modification but no proinflammatory signature.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>The transcriptome analysis of left ventricular myocardial samples from patients with HFpEF confirms an overabundant extracellular matrix gene expression, the basis of myocardial fibrosis, without a signature of activated proinflammatory pathways or genes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.123.010395","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T05:01:53Z","timestamp":1690434113000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["Left Ventricular Gene Expression in Heart Failure With Preserved Ejection Fraction\u2014Profibrotic and Proinflammatory Pathways and Genes"],"prefix":"10.1161","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1728-6506","authenticated-orcid":true,"given":"Bo","family":"Ye","sequence":"first","affiliation":[{"name":"Lillehei Heart Institute and Genomics Center of the University of Minnesota, Minneapolis (B.Y., J.E.A., M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy D.","family":"Bradshaw","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina, RHJ Department of Veterans Affairs Medical Center, Charleston (A.D.B., M.R.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9074-4307","authenticated-orcid":true,"given":"Juan E.","family":"Abrahante","sequence":"additional","affiliation":[{"name":"Lillehei Heart Institute and Genomics Center of the University of Minnesota, Minneapolis (B.Y., J.E.A., M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Dragon","sequence":"additional","affiliation":[{"name":"University of Vermont Medical Center, Cardiology, Cardiothoracic Surgery and Vermont Integrative Genomics Resource, University of Vermont, Burlington (J.A.D., T.N.H., S.P.B., F.H., M.L., M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim N.","family":"H\u00e4u\u00dfler","sequence":"additional","affiliation":[{"name":"University of Vermont Medical Center, Cardiology, Cardiothoracic Surgery and Vermont Integrative Genomics Resource, University of Vermont, Burlington (J.A.D., T.N.H., S.P.B., F.H., M.L., M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2902-7803","authenticated-orcid":true,"given":"Stephen P.","family":"Bell","sequence":"additional","affiliation":[{"name":"University of Vermont Medical Center, Cardiology, Cardiothoracic Surgery and Vermont Integrative Genomics Resource, University of Vermont, Burlington (J.A.D., T.N.H., S.P.B., F.H., M.L., M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyuki","family":"Hirashima","sequence":"additional","affiliation":[{"name":"University of Vermont Medical Center, Cardiology, Cardiothoracic Surgery and Vermont Integrative Genomics Resource, University of Vermont, Burlington (J.A.D., T.N.H., S.P.B., F.H., M.L., M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3938-3531","authenticated-orcid":true,"given":"Martin","family":"LeWinter","sequence":"additional","affiliation":[{"name":"University of Vermont Medical Center, Cardiology, Cardiothoracic Surgery and Vermont Integrative Genomics Resource, University of Vermont, Burlington (J.A.D., T.N.H., S.P.B., F.H., M.L., M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7076-221X","authenticated-orcid":true,"given":"Michael R.","family":"Zile","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina, RHJ Department of Veterans Affairs Medical Center, Charleston (A.D.B., M.R.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4398-5642","authenticated-orcid":true,"given":"Markus","family":"Meyer","sequence":"additional","affiliation":[{"name":"Lillehei Heart Institute and Genomics Center of the University of Minnesota, Minneapolis (B.Y., J.E.A., M.M.)."},{"name":"University of Vermont Medical Center, Cardiology, Cardiothoracic Surgery and Vermont Integrative Genomics Resource, University of Vermont, Burlington (J.A.D., T.N.H., S.P.B., F.H., M.L., M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.845792"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/HHF.0b013e318291329a"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001062"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.010637"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.009625"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.193326"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.587519"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.10.069"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.013215"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.052414"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.050498"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.117.004311"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.109.931451"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.02.092"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2015.10.007"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-39445-2"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.313572"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.318159"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehm037"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2010.04.004"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz401"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.TIR120.002155"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2797-4"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.045401"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-010-0706-x"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.041886"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.041657"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2014.10.003"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.311362"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00719.2017"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00274.2020"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2021.11.007"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00042"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.118.005036"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.038010"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.05.072"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/ehf2.13153"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.92.4.778"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-5223(03)00969-3"}],"container-title":["Circulation: Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCHEARTFAILURE.123.010395","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T09:12:54Z","timestamp":1749028374000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCHEARTFAILURE.123.010395"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":39,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1161\/CIRCHEARTFAILURE.123.010395"],"URL":"https:\/\/doi.org\/10.1161\/circheartfailure.123.010395","relation":{},"ISSN":["1941-3289","1941-3297"],"issn-type":[{"value":"1941-3289","type":"print"},{"value":"1941-3297","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8]]},"assertion":[{"value":"2023-01-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}