{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T11:34:51Z","timestamp":1793014491054,"version":"4.5.0"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2026,10,23]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>The cardiac sympathetic afferent reflex and pulmonary spinal afferent reflex amplify sympathetic activity and may contribute to chronic heart failure. We hypothesized that cardiac injury triggers a cardiac nerve\u2013mediated cytokine uptake cascade that propagates neural inflammation in thoracic dorsal root ganglia (DRGs) and drives reciprocal cardiopulmonary afferent sensitization through suppression of voltage-gated potassium channels after myocardial infarction (MI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>MI was induced in rats by coronary ligation. Molecular profiling, immunofluorescence, tissue clearing, and functional assays were used to assess neuroinflammation and reflex responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>Post-MI, thoracic DRGs showed macrophage infiltration, glial activation, cytokine upregulation, and reduced voltage-gated potassium channel expression. Bulk RNA-sequencing identified enrichment of macrophage activation\u2013related genes, and in vitro studies confirmed that proinflammatory cytokines and activated macrophages suppressed voltage-gated potassium channels and increased DRG neuron excitability. Epicardial injection of biotinylated TNF-\u03b1 (tumor necrosis factor-\u03b1) demonstrated cardiac afferent\u2013mediated cytokine transport to DRGs, inducing macrophage infiltration via a cytokine receptor\u2013dependent mechanism. Anti-inflammatory interventions, including oral minocycline, systemic macrophage depletion, and local epidural delivery of thermo-responsive hydrogel-forming dexamethasone prodrug (ProGel-Dex), significantly reduced DRG neuroinflammation, restored voltage-gated potassium channel levels, and attenuated exaggerated cardiac sympathetic afferent reflex and pulmonary spinal afferent reflex responses. Minocycline and ProGel-Dex also improved cardiac chamber dilation in the post-MI rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>These findings identify a neural inflammatory cascade involving cytokine uptake, glial activation, and macrophage activation as a contributor to cardiopulmonary afferent sensitization after MI. Targeting DRG inflammation, particularly with sustained dexamethasone delivery using ProGel-Dex, offers a prospect of precision medicine to dampen pathological sympathetic activation and improve cardiac outcomes in chronic heart failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.126.328216","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:00:18Z","timestamp":1790240418000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Neural Mechanisms of Heart-Lung Crosstalk in Chronic Heart Failure"],"prefix":"10.1161","volume":"139","author":[{"given":"Juan","family":"Hong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5070-5781","authenticated-orcid":true,"given":"Samuel","family":"Gillman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7880-7072","authenticated-orcid":true,"given":"Peter Ricci","family":"Pellegrino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1738-1212","authenticated-orcid":true,"given":"Rongguo","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4307-9807","authenticated-orcid":true,"given":"Steven J.","family":"Lisco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3636-7720","authenticated-orcid":true,"given":"Irving H.","family":"Zucker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8340-2763","authenticated-orcid":true,"given":"Dong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5906-8980","authenticated-orcid":true,"given":"Han-Jun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000539-200209000-00006"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.76.1.44"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198409273111303"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP284739"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-019-0221-2"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000168056.66981.c2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.03699"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1999.277.2.H812"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP273764"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1159\/000338166"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2002.007005"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2012.04.004"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a002969"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.02.028"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.807904"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-7-74"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13742"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2012.02.010"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23091"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.02.014"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2013.12.002"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.09.003"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2394-15.2016"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2014.01.019"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2021.10.007"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2024.102782"},{"key":"e_1_3_3_28_2","first-page":"40A","article-title":"Circulatory markers of nervous activation during myocardial ischemia.","author":"Malliani A","year":"1986","unstructured":"Malliani A, Lombardi F. 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