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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Chronic heart failure (CHF) is characterized by heightened cardiac sympathetic activity and neuroinflammation within the stellate ganglia (SG), contributing to cardiac arrhythmogenesis. However, the upstream mediators of this neuroimmune interaction remain incompletely defined. This study investigated whether systemic neutralization of granulocyte\u2013macrophage colony-stimulating factor (GM-CSF, an inflammatory cytokine) attenuates SG inflammation and cardiac sympathetic overactivation in a rat model of coronary artery ligation-induced CHF. Male Sprague\u2013Dawley rats underwent myocardial infarction or sham surgery and were treated with a GM-CSF neutralizing antibody or vehicle. Cardiac sympathetic nerve activity (CSNA), heart rate variability (HRV), cytokine expression, and the electrophysiological properties of cardiac sympathetic post-ganglionic (CSP) neurons were assessed. CHF increased the levels of GM-CSF, ionized calcium-binding adaptor molecule 1 (IBA1, an activated macrophage marker) and pro-inflammatory markers (TNF-\u03b1, pro IL-1\u03b2) in the SG, enhanced neuronal Ca2+ currents, cell excitability, and CSNA, and impaired HRV. The GM-CSF neutralizing antibody significantly attenuated SG inflammation, partially normalized Ca2+ currents and neuronal firing, decreased CSNA, and improved cardiac autonomic balance. These findings identify GM-CSF as a key regulator of SG neuroinflammation and sympathetic dysregulation in CHF. Targeting this GM-CSF protein may represent a novel therapeutic strategy to mitigate autonomic imbalance and arrhythmic risk.<\/jats:p>","DOI":"10.3390\/ijms27156876","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:57:56Z","timestamp":1785761876000},"page":"6876","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic Neutralization of Granulocyte\u2013Macrophage Colony-Stimulating Factor Attenuates Stellate Ganglion Neuroinflammation and Cardiac Sympathetic Overactivation in Chronic Heart Failure in Rats"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0078-3167","authenticated-orcid":false,"given":"Sulail","family":"Fatima","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68150-5850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Whitney","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68150-5850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4433-8420","authenticated-orcid":false,"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68150-5850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Shabaltiy","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68150-5850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5407-2761","authenticated-orcid":false,"given":"Yu-Long","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68150-5850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref_1","unstructured":"(2025). 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