Journal article
Genetic deletion of ASIC3 alters left ventricular remodeling and autonomic function after myocardial infarction in mice
Physiological reports, Vol.14(5), e70823
03/2026
DOI: 10.14814/phy2.70823
PMCID: PMC12976581
PMID: 41808523
Abstract
Cardiac afferent neurons have been shown to trigger overactivation of neurohormonal systems known to drive adverse cardiac remodeling following myocardial infarction (MI). Acid‐sensing ion channels (ASICs) that are highly expressed in cardiac sympathetic afferents sense ischemia‐induced 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, we induced MI 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 ischemic zone fraction, increased LV mass and wall thickness, 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 (SNA), heart rate and systolic blood pressure variability (sBPV), and hemodynamic responses to atropine and propranolol. Following MI, ASIC3−/− mice had lower baroreceptor‐renal SNA reflex sensitivity than WT mice, associated with elevated sBPV. Our data show 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. Stauss - University of IowaAnne Marie S. Harding - University of IowaMichelle C. M. Bader - University of IowaPeter 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
- Journal article
- Publication Details
- Physiological reports, Vol.14(5), e70823
- DOI
- 10.14814/phy2.70823
- PMID
- 41808523
- PMCID
- PMC12976581
- NLM abbreviation
- Physiol Rep
- ISSN
- 2051-817X
- eISSN
- 2051-817X
- Publisher
- Wiley
- Language
- English
- Date published
- 03/2026
- 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
- 9985146115002771
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