{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:32:50Z","timestamp":1787160770082,"version":"build-2736575974"},"reference-count":59,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,8,18]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">The paraventricular nucleus (PVN) of the hypothalamus is a key autonomic and cardiovascular regulatory center that contributes to neuroinflammation\u2010driven sympathetic excitation in heart failure. To define the cellular and transcriptional mechanisms underlying inflammatory signaling during heart failure progression, we performed single\u2010nucleus RNA sequencing of the PVN in rats 2\u2009weeks after myocardial infarction (MI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">PVN tissues were collected 2\u2009weeks post MI for single\u2010nucleus RNA sequencing analysis. Sequencing data were processed through alignment, dimensionality reduction, clustering, and marker\u2010gene identification to define cell populations and gene expression profiles. Gene Set Variation Analysis and transcriptional regulatory network analyses were performed to identify altered signaling pathways and key transcription factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">A total of 16\u2009341 nuclei were classified into 5 major cell types: neurons, oligodendrocytes, astrocytes, oligodendrocyte progenitor cells, and microglia. Functional analyses identified microglia as the primary mediators of inflammatory responses in the PVN. Gene Set Variation Analysis revealed substantial pathway alterations across cell types, with microglia exhibiting marked activation of immune\u2010related and cytokine\u2010producing pathways in MI rats. Moreover, IRF5 (interferon regulatory factor 5) was identified as a master transcriptional regulator associated with inflammatory activation and was significantly upregulated in PVN microglia after MI. Increased IRF5 expression in PVN microglia was confirmed by immunofluorescence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Single\u2010nucleus RNA sequencing identified distinct cell\u2010specific gene signatures, regulatory networks, and signaling pathways in the PVN during heart failure, with microglial IRF5 emerging as a central regulator of immune activation and inflammatory processes. Activated IRF5 promotes microglial activation and neuroinflammation, thereby enhancing PVN neuronal activity and driving sympathetic and neurohumoral dysregulation in rats with MI. Targeting IRF5 and its downstream pathways may therefore provide new insights into the central inflammatory mechanisms contributing to cardiac dysfunction during heart failure progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.048110","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T03:41:36Z","timestamp":1786160496000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Single\u2010Nucleus Transcriptomics Identifies Microglial Interferon Regulatory Factor 5 as a Regulator of Neuroinflammation During Heart Failure Progression After Myocardial Infarction in Rats"],"prefix":"10.1161","volume":"15","author":[{"given":"Wanxin","family":"Tang","sequence":"first","affiliation":[{"name":"University of Iowa","place":["Iowa City, 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