{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T19:36:28Z","timestamp":1792870588673,"version":"4.5.0"},"reference-count":28,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["OMICS: A Journal of Integrative Biology"],"published-print":{"date-parts":[[2026,12,1]]},"abstract":"<jats:p>Heart failure with preserved ejection fraction (HFpEF) involves interacting immune, vascular, and stromal abnormalities. We asked whether macrophage genes showing opposite diet-associated and dapagliflozin-associated effects could identify regulatory and signaling programs relevant to HFpEF. Genes were ranked in a 2 \u00d7 2 \u00d7 2 dataset of sorted murine cardiac macrophages, and the locked signatures were evaluated in cardiac single-cell and single-nucleus datasets. Regulon analysis and network-constrained sensitivity testing identified BHLHE40 as the more robust program-level candidate. NFKB1, in turn, was linked to the broadest curated communication network, including TNF-, IL1B-, and PDGFB-related endothelial and fibroblast branches. External evidence varied across datasets and cell compartments. In myocardium from 19 HFpEF and 24 control donors, the CCR2\u2212 and cross-subset signatures were higher in macrophages, and the CCR2\u2212 signature was also higher in fibroblasts. PDGFB-related fibroblast branches received broader external evidence than the discovery-ranked TNF\u2013TNFRSF1A endothelial branch, whose direction was not retained in human myocardium. These results nominate testable macrophage regulatory and signaling hypotheses for HFpEF but do not establish drug-specific reversal or cross-model conservation.<\/jats:p>","DOI":"10.1177\/15578100261479258","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:39:47Z","timestamp":1786966787000},"page":"745-757","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Transcriptomics Links Dapagliflozin-Opposed Macrophage Programs to BHLHE40-Associated Regulation and NFKB1-Associated Signaling in HFpEF"],"prefix":"10.1177","volume":"30","author":[{"given":"Dingkun","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyao","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruonan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, The 908th Hospital of the Joint Logistic Support Force, Nanchang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Wuhan Asia Heart Hospital, Wuhan, China."},{"name":"School of Medicine, Wuhan University of Science and Technology, Wuhan, 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