{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T05:19:25Z","timestamp":1787721565157,"version":"build-2784847793"},"reference-count":51,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01HL172029"],"award-info":[{"award-number":["R01HL172029"]}]},{"name":"NIH","award":["P01 HL62222"],"award-info":[{"award-number":["P01 HL62222"]}]},{"name":"Theodore F. Hubbard Family Foundation"},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["#18POST34030046"],"award-info":[{"award-number":["#18POST34030046"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]},{"award":["#18POST34030046"],"award-info":[{"award-number":["#18POST34030046"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Chronic heart failure (CHF) is a growing global health concern characterized, in part, by progressive sympathetic overactivation, which exacerbates this condition. Accumulating evidence identifies oxidative stress as a key driver of sympatho-excitation, mediated by excess reactive oxygen species (ROS) and impaired antioxidant defenses. The redox-sensitive transcription factor nuclear factor erythroid 2\u2013related factor 2 (Nrf2) is a central regulator of antioxidant gene expression, but its role in the peripheral sympathetic nervous system, particularly in the stellate ganglia, remains unclear. We hypothesized that Nrf2 signaling is disrupted in the stellate ganglia in CHF and that modulation of Nrf2 alters ROS levels and sympathetic responses. In rats, six weeks post myocardial infarction (MI), the stellate ganglia exhibited increased ROS levels in tyrosine hydroxylase-positive neurons along with reduced Nrf2 protein and mRNA expression; both changes were inversely associated with ejection fraction (EF). To determine the functional role of Nrf2, lentiviral vectors encoding GFP or GFP-Nrf2 were delivered to the stellate ganglia three weeks after MI. Nrf2 upregulation attenuated heart rate responses to stellate stimulation in sham rats but augmented responses in CHF rats. The increase in plasma norepinephrine levels was reduced following stellate stimulation in CHF rats that overexpressed Nrf2, while \u03b21-adrenergic responsiveness to dobutamine was unchanged. This study demonstrates that CHF is associated with increased oxidative stress and reduced Nrf2 expression in the stellate ganglion. Nrf2 overexpression significantly modulated sympathetic regulation, altering heart rate responses and reducing plasma norepinephrine in CHF rats. These findings support the concept that impaired Nrf2 signaling contributes to ganglionic redox imbalance and dysregulated sympathetic nerve activity in CHF.<\/jats:p>","DOI":"10.3390\/antiox15091054","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:03:41Z","timestamp":1787558621000},"page":"1054","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Stellate Ganglion Nrf2 Modulates Oxidative Stress and Heart Rate Responses in Mice and Rats with Heart Failure"],"prefix":"10.3390","volume":"15","author":[{"given":"Julia","family":"Shanks","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medical and Health Sciences, Manaaki Manawa the Centre for Heart Research, University of Auckland, Auckland 1010, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0853-5758","authenticated-orcid":false,"given":"Neha","family":"Dhyani","sequence":"additional","affiliation":[{"name":"Department Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3327-6366","authenticated-orcid":false,"given":"Tara L.","family":"Rudebush","sequence":"additional","affiliation":[{"name":"Department Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7880-7213","authenticated-orcid":false,"given":"Lie","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5906-8980","authenticated-orcid":false,"given":"Hanjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3636-7720","authenticated-orcid":false,"given":"Irving H.","family":"Zucker","sequence":"additional","affiliation":[{"name":"Department Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e67","DOI":"10.1161\/CIR.0000000000000558","article-title":"Heart disease and stroke statistics\u20142018 update: A report from the American Heart Association","volume":"137","author":"Benjamin","year":"2018","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e139","DOI":"10.1161\/CIR.0000000000000757","article-title":"Heart disease and stroke statistics\u20142020 update: A report from the American Heart Association","volume":"141","author":"Virani","year":"2020","journal-title":"Circulation"},{"key":"ref_3","first-page":"S210","article-title":"Experimental models of heart failure: Implications for renin and the kidney","volume":"20","author":"Riegger","year":"1987","journal-title":"Kidney Int. 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