{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:01:34Z","timestamp":1782280894436,"version":"3.54.5"},"posted":{"date-parts":[[2025,9,8]]},"group-title":"Physiology","reference-count":73,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Chronic overactivation of neurohormonal systems is the principal driver of adverse cardiac remodeling following myocardial infarction (MI). Recent data suggest that ablating cardiac afferent neurons in rats attenuates left ventricular (LV) remodeling following MI by blocking this overactivation. Our lab has shown that acid-sensing ion channels (ASICs) are highly expressed in cardiac afferents and may sense myocardial acidosis. We hypothesized that genetic deletion of ASICs might abrogate disadvantageous remodeling after MI by disrupting afferent signaling pathways otherwise resulting in overactivation of neurohormonal responses. To test this hypothesis, we induced MI by coronary artery ligation in wild type (WT) and ASIC3\n                  <jats:sup>-\/-<\/jats:sup>\n                  mice and assessed cardiac remodeling by serial echocardiography. We found that ASIC3\n                  <jats:sup>-\/-<\/jats:sup>\n                  mice had less LV dilation relative to MI size, increased LV mass, and increased stroke volume compared to WT mice after MI. To investigate a potential role of the autonomic nervous system, we measured renal and splanchnic sympathetic nerve activity, heart rate and systolic blood pressure variability (sBPV), and hemodynamic responses to atropine and propranolol. In addition, we assessed baroreceptor-heart rate and baroreceptor-renal sympathetic nerve activity (RSNA) reflex function. Following MI, ASIC3\n                  <jats:sup>-\/-<\/jats:sup>\n                  mice had lower baroreceptor-RSNA reflex sensitivity than WT mice, associated with elevated sBPV. Importantly, sBPV correlated significantly with post-MI changes in LV mass in ASIC3\n                  <jats:sup>-\/-<\/jats:sup>\n                  but not WT mice. Our data shows that ASIC3 plays an important role in cardiac remodeling after MI potentially via modulation of baroreflex sensitivity and sBPV. ASIC3 may be further investigated as a potential therapeutic target in heart failure.\n                <\/jats:p>","DOI":"10.1101\/2025.09.03.674120","type":"posted-content","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T16:10:18Z","timestamp":1757347818000},"source":"Crossref","is-referenced-by-count":0,"title":["Genetic Deletion of ASIC3 Alters Left Ventricular Remodeling and Autonomic Function After Myocardial Infarction in Mice"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5479-4024","authenticated-orcid":false,"given":"Karley M.","family":"Monaghan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D.","family":"Gibbons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad C.","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maram","family":"El-Geneidy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Kutschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy A.","family":"Zimmerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3167-1643","authenticated-orcid":false,"given":"Donald A.","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald M.","family":"Stauss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Marie S.","family":"Harding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle C. 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