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Exogenous high-mobility group box 1 improves myocardial recovery after acute global ischemia/reperfusion injury
Aaron M Abarbanell1, Jacob A Hartley, Jeremy L Herrmann
1Department of Surgery, Indiana University, 2017 Van Nuys Medical Science Building, 635 Barnhill Drive, Indianapolis, IN 46202, USA.
Insights
Low-dose high-mobility group box 1 (HMGB1) therapy improved heart function and reduced infarct size after global ischemia/reperfusion (I/R) injury. This cardioprotective effect was linked to suppressed inflammation, suggesting HMGB1 as a potential therapeutic agent.
Area of Science:
- Cardiology
- Molecular Biology
- Inflammation Research
Background:
- High-mobility group box 1 (HMGB1) is a known inflammation mediator with dose-dependent effects on myocardial function.
- While high-dose HMGB1 impairs function in regional myocardial infarction, its role in global ischemia/reperfusion (I/R) injury remains unclear.
Purpose of the Study:
- To investigate the effect of low-dose high-mobility group box 1 (HMGB1) on myocardial functional recovery and infarct size following global ischemia/reperfusion (I/R) injury.
- To explore the association between HMGB1 treatment, cardioprotective paracrine factors, and inflammation modulation in the context of I/R injury.
Main Methods:
- Isolated adult rat hearts underwent global I/R using the Langendorff method.
- Hearts were treated with either vehicle, 200-ng HMGB1, or 1-μg HMGB1 at the onset of reperfusion.
- Myocardial function, infarct size, and levels of inflammatory cytokines and growth factors were assessed.
Main Results:
- Treatment with 200-ng HMGB1 significantly enhanced myocardial functional recovery post-I/R.
- This improvement was associated with a reduced infarct size and decreased levels of IL-1, IL-6, IL-10, and VEGF.
- Higher dose (1-μg HMGB1) reduced inflammation but did not improve functional recovery.
Conclusions:
- Postischemic administration of 200-ng HMGB1 effectively improves cardiac function and reduces infarct size in global I/R injury.
- The cardioprotective effects are linked to suppressed myocardial inflammation.
- Exogenous HMGB1 shows promise as a therapeutic strategy for acute postischemic conditions.
Background:
High-mobility group box 1 (HMGB1) is a mediator of inflammation with dose-dependent effects. In the setting of regional myocardial infarction, a high-dose HMGB1 treatment decreases myocardial function, whereas low-dose HMGB1 improves function; however, it is unknown what role HMGB1 has in the setting of global ischemia/reperfusion (I/R) injury. We hypothesized that a low-dose HMGB1 treatment would improve myocardial functional recovery and decrease infarct size after global I/R injury in association with increased levels of cardioprotective paracrine factors and decreased inflammation.
Methods:
Adult rat hearts were isolated and perfused using the Langendorff method and were subjected to global I/R and treatment with either the vehicle, 200-ng HMGB1, or 1-μg HMGB1. The treatment was administered during 1 min at the start of reperfusion, and myocardial function was measured for 60 min of reperfusion. At the end of reperfusion, the hearts were sectioned and incubated in triphenyltetrazolium chloride to assess myocardial infarct size or homogenized to measure levels of inflammatory cytokines and growth factors.
Results:
Postischemic treatment with 200-ng HMGB1 significantly improved myocardial functional recovery after global I/R in association with decreased infarct size and decreased interleukin-1 (IL-1), IL-6, IL-10, and vascular endothelial growth factor (VEGF) levels. In addition, 1-μg HMGB1 decreased myocardial inflammation but did not result in subsequent improvement in functional recovery.
Conclusion:
In the setting of global I/R, 200-ng postischemic HMGB1 treatment improves myocardial function and decreases infarct size in association with suppressed myocardial inflammation. These results suggest a potential role for exogenous HMGB1therapy in the acute postischemic period.
