An apoptosis signal-regulating kinase 1 inhibitor reduces cardiomyocyte apoptosis and infarct size in a rat ischemia-reperfusion model.
J Cardiovasc Pharmacol
; 60(3): 276-82, 2012 Sep.
Article
em En
| MEDLINE
| ID: mdl-22635076
ABSTRACT
PURPOSES:
We determined whether a small molecule inhibitor of apoptosis signal-regulating kinase 1 (ASK1-i) could reduce myocardial infarct size in a rat ischemia/reperfusion model. METHODS ANDRESULTS:
Sprague-Dawley rats were randomized to 3 groups ASK1-i infusion (n = 16), vehicle infusion (n = 16), or ischemic preconditioning (IPC; n = 15). Infusion of ASK1-i (10 mg/kg, iv) or vehicle commenced 45 minutes before myocardial ischemia. IPC consisted of 3 cycles of 3 minutes of coronary occlusion followed by 5 minutes of reperfusion immediately before index myocardial ischemia, which consisted of 30-minute left coronary occlusion followed by 180 minutes of reperfusion. Pathologic analysis revealed no significant difference in the ischemic risk size among the 3 groups. ASK1-I and IPC significantly reduced myocardial infarct size (27.7% ± 3.3%, 16.5% ± 3.4%, and 41.5% ± 4.8% in the ASK1-i group, the IPC group, and the vehicle group, respectively; P = 0.0002) and apoptosis (the percentage of apoptotic nuclei averaged 11.6% ± 1.0%, 10.2% ± 1.7%, and 17.7% ± 2.0% in the ASK1-i group, IPC group, and vehicle group, respectively, P = 0.0055).CONCLUSIONS:
A small molecule inhibitor of ASK1 was shown for the first time to reduce apoptosis and myocardial infarct size in a rat model of ischemia/reperfusion.
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Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão Miocárdica
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Apoptose
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MAP Quinase Quinase Quinase 5
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Inibidores de Proteínas Quinases
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Modelos Animais de Doenças
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Infarto do Miocárdio
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article