Cooperation of the two interferon-inducible transcription factors STAT1 and IRF1 in the pathogenesis of acute myocardial infarction

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One of the major therapeutic challenges of modern cardiology is to design efficacious strategies aimed at minimizing myocardial necrosis and optimizing cardiac repair mechanisms following acute myocardial infarction. Inflammation, including the recruitment of neutrophils and macrophages to the infarcted area, is a hallmark feature of myocardial ischemia which contributes to myocardial injury. The inflammatory reaction triggered by the local release of cytokines such as interferons is a prerequisite for tissue repair but also the cause of scar formation in the ischemic heart tissue. The two interferon-dependent transcription factors STAT1 (signal transducer and activator of transcription 1) and IRF1 (interferon-regulatory factor 1) are involved in the regulation of inflammatory reactions. However, their roles in the infarcted myocardium following permanent or transient occlusion of a coronary artery have not been systematically investigated in an organismic context. Using transgenic mouse models, we aimed at studying the functional cooperativity of the two interferon-inducible transcription factors in the control of inflammatory infiltrates in infarcted areas. From the proposed project, we expect insights into the pathogenesis of myocardial infarction which may help to identify novel targets for future pharmacological interventions.