Background: Interleukin-1α (IL-1α) released by dying cells is an alarmin that activates the innate immunity. We hypothesized that after myocardial ischemia-reperfusion (I/R) injury, IL-1α amplifies the myocardial damage by activating the inflammasome and caspase-1. Methods: Adult male CD1 mice were used. The left anterior descending coronary artery was ligated for 30 minutes, after 24 hours of reperfusion. An IL-1α blocking antibody (15 μg/kg intraperitoneally) or matching vehicle was given after reperfusion. A subgroup of mice underwent sham surgery. We assessed the effects of IL-1α blockade on caspase-1 activity, infarct size, cardiac troponin I serum levels, and left ventricular fractional shortening, 24 hours after I/R. Results: I/R led to inflammasome formation, and IL-1α blockade significantly reduced inflammasome formation, reflected by a >50% reduction in caspase-1 activity versus vehicle (P = 0.03). IL-1α blockade also reduced the infarct size (-52% infarct expressed as percentage of area at risk, and-79% for cardiac troponin I serum levels, P < 0.001 vs. vehicle) and preserved the left ventricular fractional shortening (31 ± 3% vs. 25 ± 2%, P < 0.001 vs. vehicle). Conclusion: IL-1α blockade after I/R reduces the inflammasome activation, decreases the infarct size, and preserves the left ventricular function. IL-1α blockade may therefore represent a novel therapeutic strategy to reduce I/R injury.

Reduction of Myocardial Ischemia-Reperfusion Injury by Inhibiting Interleukin-1 Alpha / Mauro, ADOLFO GABRIELE; Mezzaroma, Eleonora; Torrado, Juan; Kundur, Priyanka; Joshi, Priyashma; Stroud, Kelsey; Quaini, Federico; Lagrasta, Costanza Anna Maria; Abbate, Antonio; Toldo, Stefano. - In: JOURNAL OF CARDIOVASCULAR PHARMACOLOGY. - ISSN 0160-2446. - 69:3(2017), pp. 156-160. [10.1097/FJC.0000000000000452]

Reduction of Myocardial Ischemia-Reperfusion Injury by Inhibiting Interleukin-1 Alpha

MAURO, ADOLFO GABRIELE;QUAINI, Federico;LAGRASTA, Costanza Anna Maria;
2017-01-01

Abstract

Background: Interleukin-1α (IL-1α) released by dying cells is an alarmin that activates the innate immunity. We hypothesized that after myocardial ischemia-reperfusion (I/R) injury, IL-1α amplifies the myocardial damage by activating the inflammasome and caspase-1. Methods: Adult male CD1 mice were used. The left anterior descending coronary artery was ligated for 30 minutes, after 24 hours of reperfusion. An IL-1α blocking antibody (15 μg/kg intraperitoneally) or matching vehicle was given after reperfusion. A subgroup of mice underwent sham surgery. We assessed the effects of IL-1α blockade on caspase-1 activity, infarct size, cardiac troponin I serum levels, and left ventricular fractional shortening, 24 hours after I/R. Results: I/R led to inflammasome formation, and IL-1α blockade significantly reduced inflammasome formation, reflected by a >50% reduction in caspase-1 activity versus vehicle (P = 0.03). IL-1α blockade also reduced the infarct size (-52% infarct expressed as percentage of area at risk, and-79% for cardiac troponin I serum levels, P < 0.001 vs. vehicle) and preserved the left ventricular fractional shortening (31 ± 3% vs. 25 ± 2%, P < 0.001 vs. vehicle). Conclusion: IL-1α blockade after I/R reduces the inflammasome activation, decreases the infarct size, and preserves the left ventricular function. IL-1α blockade may therefore represent a novel therapeutic strategy to reduce I/R injury.
Reduction of Myocardial Ischemia-Reperfusion Injury by Inhibiting Interleukin-1 Alpha / Mauro, ADOLFO GABRIELE; Mezzaroma, Eleonora; Torrado, Juan; Kundur, Priyanka; Joshi, Priyashma; Stroud, Kelsey; Quaini, Federico; Lagrasta, Costanza Anna Maria; Abbate, Antonio; Toldo, Stefano. - In: JOURNAL OF CARDIOVASCULAR PHARMACOLOGY. - ISSN 0160-2446. - 69:3(2017), pp. 156-160. [10.1097/FJC.0000000000000452]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2824956
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