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Sensory Neurons Release Cardioprotective Factors in an In Vitro Ischemia Model
Clara Hoebart1, Attila Kiss2, Bruno K Podesser2
1Institute of Physiology, Center for Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria.
Biomedicines
|August 29, 2024
Summary
Sensory neurons protect heart cells from damage during ischemia. They secrete cardioprotective substances that enhance survival, offering potential therapeutic targets for heart conditions.
Area of Science:
- Cardiovascular Biology
- Neurocardiology
- Cellular Physiology
Background:
- Sensory neurons extensively innervate the heart muscle (myocardium).
- The function of sensory neurons in sensing and responding to myocardial ischemia and reperfusion is not well understood.
- Previous studies suggest sensory neurons may enhance cardiomyocyte survival during injury.
Purpose of the Study:
- To investigate the role of sensory neurons in protecting cardiomyocytes from ischemia-reperfusion (I/R) injury.
- To identify potential cardioprotective factors secreted by sensory neurons.
- To elucidate the mechanism by which sensory neurons confer protection to cardiomyocytes.
Main Methods:
- A cellular model of I/R injury was used, involving primary murine cardiomyocytes and sensory neurons.
- Sensory neurons were subjected to ischemia, and the resulting conditioned supernatant was applied to cardiomyocytes.
- Protease activity, ultracentrifugation (to remove extracellular vesicles), and fractionation were used to characterize the protective agent.
- Metabolomic analysis was performed to identify changes in metabolites and lipids.
Main Results:
- Conditioned supernatant from ischemic sensory neurons significantly increased cardiomyocyte tolerance to I/R injury.
- The protective effect was lost upon significant dilution, indicating a substance present in the supernatant.
- The protective effect was retained after removing extracellular vesicles and was not degraded by proteases.
- Fractionation suggested the active agent is hydrophilic.
- Metabolomic analysis revealed 64 significantly altered metabolites and lipids.
- Other cell types (HEK293t, 3T3 fibroblasts) also conferred protection, but to a lesser extent.
Conclusions:
- Sensory neurons secrete one or more hydrophilic cardioprotective substances.
- These secreted substances enhance cardiomyocyte survival during I/R injury.
- The findings suggest a novel mechanism of neuro-cardiac protection involving secreted factors, potentially useful for therapeutic development.
