{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T12:04:22Z","timestamp":1770897862150,"version":"3.50.1"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T00:00:00Z","timestamp":1654214400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["FP7\u2010242209\u2010BIOSTAT\u2010CHF"],"award-info":[{"award-number":["FP7\u2010242209\u2010BIOSTAT\u2010CHF"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Heart Fail"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Chronic heart failure (CHF) is a systemic syndrome with a poor prognosis and a need for novel therapies. We investigated whether whole blood transcriptomic profiling can provide new mechanistic insights into cardiovascular (CV) mortality in CHF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      Transcriptome profiles were generated at baseline from 944 CHF patients from the BIOSTAT\u2010CHF study, of whom 626 survived and 318 died from a CV cause during a follow\u2010up of 21\u2009months. Multivariable analysis, including adjustment for cell count, identified 1153 genes (6.5%) that were differentially expressed between those that survived or died and strongly related to a validated clinical risk score for adverse prognosis. The differentially expressed genes mainly belonged to five non\u2010redundant pathways: adaptive immune response, proteasome\u2010mediated ubiquitin\u2010dependent protein catabolic process, T\u2010cell co\u2010stimulation, positive regulation of T\u2010cell proliferation, and erythrocyte development. These five pathways were selectively related (RV coefficients &gt;0.20) with seven circulating protein biomarkers of CV mortality (fibroblast growth factor 23, soluble ST2, adrenomedullin, hepcidin, pentraxin\u20103, WAP 4\u2010disulfide core domain 2, and interleukin\u20106) revealing an intricate relationship between immune and iron homeostasis. The pattern of survival\u2010associated gene expression matched with 29 perturbagen\u2010induced transcriptome signatures in the iLINCS drug\u2010repurposing database, identifying drugs, approved for other clinical indications, that were able to reverse\n                      <jats:italic>in vitro<\/jats:italic>\n                      the molecular changes associated with adverse prognosis in CHF.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Systematic modelling of the whole blood protein\u2010coding transcriptome defined molecular pathways that provide a link between clinical risk factors and adverse CV prognosis in CHF, identifying both established and new potential therapeutic targets.<\/jats:p>\n                  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