RGD Reference Report - An apoptosis signal-regulating kinase 1 inhibitor reduces cardiomyocyte apoptosis and infarct size in a rat ischemia-reperfusion model. - Rat Genome Database

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An apoptosis signal-regulating kinase 1 inhibitor reduces cardiomyocyte apoptosis and infarct size in a rat ischemia-reperfusion model.

Authors: Gerczuk, PZ  Breckenridge, DG  Liles, JT  Budas, GR  Shryock, JC  Belardinelli, L  Kloner, RA  Dai, W 
Citation: Gerczuk PZ, etal., J Cardiovasc Pharmacol. 2012 Sep;60(3):276-82. doi: 10.1097/FJC.0b013e31825ea0fa.
RGD ID: 10412335
Pubmed: PMID:22635076   (View Abstract at PubMed)
DOI: DOI:10.1097/FJC.0b013e31825ea0fa   (Journal Full-text)

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 AND RESULTS: 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
myocardial infarction treatmentISOMap3k5 (Rattus norvegicus)10412335; 10412335 RGD 
myocardial infarction treatmentIMP 10412335 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of cardiac muscle cell apoptotic process  IMP 10412335 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Map3k5  (mitogen-activated protein kinase kinase kinase 5)

Genes (Mus musculus)
Map3k5  (mitogen-activated protein kinase kinase kinase 5)

Genes (Homo sapiens)
MAP3K5  (mitogen-activated protein kinase kinase kinase 5)


Additional Information