Preprint
Genetic Deletion of ASIC3 Alters Left Ventricular Remodeling and Autonomic Function After Myocardial Infarction in Mice
bioRxiv
Cold Spring Harbor Laboratory
09/08/2025
DOI: 10.1101/2025.09.03.674120
PMCID: PMC12440009
PMID: 40964271
Abstract
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
mice and assessed cardiac remodeling by serial echocardiography. We found that ASIC3
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
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
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.
Details
- Title: Subtitle
- Genetic Deletion of ASIC3 Alters Left Ventricular Remodeling and Autonomic Function After Myocardial Infarction in Mice
- Creators
- Karley M Monaghan - University of IowaDavid D Gibbons - University of IowaChad C Ward - University of IowaMaram El-Geneidy - University of IowaWilliam J Kutschke - University of IowaKathy A Zimmerman - University of IowaDonald A Morgan - University of IowaHarald M StaussAnne Marie S Harding - University of IowaMichelle C M BaderPeter M Snyder - University of IowaRasna Sabharwal - University of IowaRobert M Weiss - University of IowaKamal Rahmouni - University of IowaChristopher J Benson - University of Iowa
- Resource Type
- Preprint
- Publication Details
- bioRxiv
- DOI
- 10.1101/2025.09.03.674120
- PMID
- 40964271
- PMCID
- PMC12440009
- NLM abbreviation
- bioRxiv
- ISSN
- 2692-8205
- eISSN
- 2692-8205
- Publisher
- Cold Spring Harbor Laboratory; United States
- Language
- English
- Date posted
- 09/08/2025
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Medicine Administration; Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984964238602771
Metrics
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