Background Successful reperfusion is the most effective strategy to reduce ischemic injury in acute myocardial infarction (AMI). Ischemic injury, however, also triggers a secondary ischemia-independent injury, known as reperfusion injury, contributing to the overall infarct size. We hypothesize that inhibition of the Nod-like Receptor Protein-3 (NLRP3) inflammasome limits infarct size following myocardial ischemia/reperfusion (I/R), by inhibiting the inflammatory component of the reperfusion injury. Methods CD-1 male mice underwent transient ligation of the left anterior descending coronary artery for 30 or 75 min followed by reperfusion. Infarct size was measured at 1, 3 and 24 h. A NLRP3 inflammasome inhibitor (NLRP3inh) or vehicle was administrated immediately at time of reperfusion or with a delay of 1 or 3 h of reperfusion. Results A time-dependent increase in infarct size was measured at 1, 3, and 24 h after reperfusion (11 ± 2%, 30 ± 5% and 43 ± 4% of the area at risk respectively; P < 0.001 for trend). NLRP3 myocardial expression was significantly increased at 24 h and 6 h vs 3 h (P < 0.01). Administration of the NLRP3inh at reperfusion did not reduce infarct size at 3 h, while it significantly reduced infarct size at 24 h (- 56% vs vehicle, P < 0.01). The NLRP3inh given 1 h after reperfusion also significantly decreased caspase-1 activity and infarct size measured at 24 h, whereas the NLRP3inh did not when given with a delay of 3 h. Conclusions Pharmacological inhibition of the NLRP3 inflammasome within 1 h of reperfusion limits the secondary inflammatory injury and infarct size following myocardial ischemia-reperfusion in the mouse.

Inhibition of the NLRP3 inflammasome limits the inflammatory injury following myocardial ischemia-reperfusion in the mouse / Toldo, Stefano; Marchetti, Carlo; Mauro, Adolfo G.; Chojnacki, Jeremy; Mezzaroma, Eleonora; Carbone, Salvatore; Zhang, Shijun; Van Tassell, Benjamin; Salloum, Fadi N.; Abbate, Antonio. - In: INTERNATIONAL JOURNAL OF CARDIOLOGY. - ISSN 0167-5273. - 209:(2016), pp. 215-220. [10.1016/j.ijcard.2016.02.043]

Inhibition of the NLRP3 inflammasome limits the inflammatory injury following myocardial ischemia-reperfusion in the mouse

Carbone, Salvatore;Abbate, Antonio
2016

Abstract

Background Successful reperfusion is the most effective strategy to reduce ischemic injury in acute myocardial infarction (AMI). Ischemic injury, however, also triggers a secondary ischemia-independent injury, known as reperfusion injury, contributing to the overall infarct size. We hypothesize that inhibition of the Nod-like Receptor Protein-3 (NLRP3) inflammasome limits infarct size following myocardial ischemia/reperfusion (I/R), by inhibiting the inflammatory component of the reperfusion injury. Methods CD-1 male mice underwent transient ligation of the left anterior descending coronary artery for 30 or 75 min followed by reperfusion. Infarct size was measured at 1, 3 and 24 h. A NLRP3 inflammasome inhibitor (NLRP3inh) or vehicle was administrated immediately at time of reperfusion or with a delay of 1 or 3 h of reperfusion. Results A time-dependent increase in infarct size was measured at 1, 3, and 24 h after reperfusion (11 ± 2%, 30 ± 5% and 43 ± 4% of the area at risk respectively; P < 0.001 for trend). NLRP3 myocardial expression was significantly increased at 24 h and 6 h vs 3 h (P < 0.01). Administration of the NLRP3inh at reperfusion did not reduce infarct size at 3 h, while it significantly reduced infarct size at 24 h (- 56% vs vehicle, P < 0.01). The NLRP3inh given 1 h after reperfusion also significantly decreased caspase-1 activity and infarct size measured at 24 h, whereas the NLRP3inh did not when given with a delay of 3 h. Conclusions Pharmacological inhibition of the NLRP3 inflammasome within 1 h of reperfusion limits the secondary inflammatory injury and infarct size following myocardial ischemia-reperfusion in the mouse.
2016
infarction; inflammasome; inflammation; injury; ischemia; reperfusion
01 Pubblicazione su rivista::01a Articolo in rivista
Inhibition of the NLRP3 inflammasome limits the inflammatory injury following myocardial ischemia-reperfusion in the mouse / Toldo, Stefano; Marchetti, Carlo; Mauro, Adolfo G.; Chojnacki, Jeremy; Mezzaroma, Eleonora; Carbone, Salvatore; Zhang, Shijun; Van Tassell, Benjamin; Salloum, Fadi N.; Abbate, Antonio. - In: INTERNATIONAL JOURNAL OF CARDIOLOGY. - ISSN 0167-5273. - 209:(2016), pp. 215-220. [10.1016/j.ijcard.2016.02.043]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1021227
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