Alpha-1 antitrypsin inhibits caspase-1 and protects from acute myocardial ischemia-reperfusion injury

Stefano Toldo, Ignacio M. Seropian, Eleonora Mezzaroma, Benjamin W. Van Tassell, Fadi N. Salloum, Eli C. Lewis, Norbert Voelkel, Charles A. Dinarello, Antonio Abbate

Research output: Contribution to journalArticlepeer-review

117 Scopus citations


Alpha-1-antitrypsin (AAT) possesses anti-inflammatory and tissue-protective properties. Here, we studied the effects of exogenously administered AAT on caspase-1 activity and on the outcome of ischemia-reperfusion injury (I/R) in a mouse model of acute myocardial infarction (AMI). Adult male mice underwent 30. min of coronary artery ligation followed by reperfusion and were randomly assigned to receive clinical-grade AAT or albumin at reperfusion. Infarct size was evaluated after 1 and 7. days. Caspase-1 activity was measured in homogenates of heart tissue. Left ventricular (LV) end-diastolic diameter (EDD) and end-systolic diameter (ESD) were measured and LV fractional shortening (FS) and ejection fraction (EF) were calculated using transthoracic echocardiography. The effect of AAT on caspase-1 activity was determined in cultures of mouse HL-1 cardiomyocytes stimulated with LPS and triggered with nigericin or when HL-1 cells were exposed to simulated ischemia. AAT-treated mice had significantly smaller infarct sizes (-30% day 1 and -55% day 7) compared with mice treated with albumin. AAT treatment resulted in > 90% reduction in caspase-1 activity in homogenates of hearts 24. h after I/R. Seven days after AMI, AAT-treated mice exhibited a > 90% smaller increase in LVEDD and LVESD and smaller reduction in LVEF. The increase in caspase-1 activity in HL-1 cells induced by LPS and nigericin or following exposure to simulated ischemia was reduced by > 80% and AAT similarly reduced cell death by > 50%. In conclusion, exogenous administration of clinical grade AAT reduces caspase-1 activity in the ischemic myocardium leading to preservation of viable myocardium and prevention of adverse cardiac remodeling.

Original languageEnglish
Pages (from-to)244-251
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Issue number2
StatePublished - 1 Aug 2011
Externally publishedYes


  • Caspase-1
  • Cell death
  • Inflammation
  • NEW-Myocardial infarction
  • NEW-Remodeling

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine


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