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Catecholamine-Induced Inflammasome Activation in the Heart Following Photothrombotic Stroke
Xavier O Scott1, Nadine A Kerr2,3, Juliana Sanchez-Molano2,3
1Department of Molecular Physiology and Cellular Biophysics, University of Miami Miller School of Medicine, Miami, FL, USA.
Insights
Stroke triggers a catecholamine surge, activating the AIM2 inflammasome in the heart. This inflammasome activation and subsequent pyroptosis contribute to cardiac dysfunction, but can be blocked by the inhibitor IC100.
Area of Science:
- Neuroscience
- Cardiology
- Immunology
Background:
- Cerebrovascular stroke patients often experience cardiac arrhythmias.
- Post-traumatic cardiac dysfunction is linked to catecholamine surges and inflammation.
- The role of inflammasome activation in post-stroke cardiac dysfunction is unknown.
Purpose of the Study:
- Investigate inflammasome activation in post-stroke cardiac dysfunction.
- Determine the role of catecholamines in this process.
- Evaluate the efficacy of the inflammasome inhibitor IC100.
Main Methods:
- Used a mouse model of photothrombotic stroke (PTS).
- Administered epinephrine to induce catecholamine surge.
- Recorded action potential duration in excised zebrafish hearts.
- Assessed inflammasome markers (AIM2, IL-1b, caspase-8).
Main Results:
- PTS induced AIM2 inflammasome activation in mouse atria and ventricles.
- Epinephrine injection increased AIM2, IL-1b, and caspase-8 in mouse atria.
- Epinephrine shortened action potential duration in zebrafish hearts.
- IC100 treatment reduced inflammasome activation and protected cardiac function.
Conclusions:
- Stroke-induced catecholamine surge activates the AIM2 inflammasome and pyroptosis in the heart.
- This pathway contributes to cardiac dysfunction after stroke.
- IC100 effectively blocks inflammasome activation, offering a therapeutic strategy for stroke-related cardiovascular injury.
Abstract:
Cerebrovascular stroke patients exhibit an increased incidence of cardiac arrhythmias. The pathomechanisms underlying post-traumatic cardiac dysfunction include a surge of catecholamines and an increased systemic inflammatory response, but whether inflammasome activation contributes to cardiac dysfunction remains unexplored. Here, we used a mouse model of photothrombotic stroke (PTS) to investigate the role of inflammasome activation in post-stroke cardiac dysfunction by catecholamines and to evaluate the effectiveness of the inflammasome inhibitor IC100 on inflammasome activation. To evaluate functional electrophysiological changes in the heart by catecholamine treatment, we recorded action potential duration in excised zebrafish hearts with and without IC100 treatment. We show that PTS induced AIM2 inflammasome activation in atria and ventricles that was significantly reduced by administration of IC100. Injection of epinephrine into naïve mice induced a significant increase in AIM2, IL-1b and caspase-8 in atria. Treatment of excised zebrafish hearts with epinephrine shortened the action potential duration and this shortening that was reduced by IC100. These findings indicate that stroke initiates a catecholamine surge that induces inflammasome activation and pyroptosis in the heart that is blocked by IC100, thus providing a framework for the development of therapeutics for stroke-related cardiovascular injury.
