Cardiac Critical Care Research Program
Peri-operative myocardial ischemia and infarction (heart attack) represents the major cause of morbidity and mortality for the large number of surgical patients who undergoes a variety of operations such as heart transplantation, coronary artery bypass grafting, and revascularization. Because injured cardiac tissues after a heart attack typically cannot regenerate, ischemic myocardial injury often leads to deterioration of myocardial function and death. Therefore, it is critically important and clinically relevant to understand the molecular mechanisms governing ischemic myocardial injury and identify potential targets for intervention.
Cardiomyocyte death and myocardial inflammation can both contribute to ischemic myocardial infarction and left ventricular dysfunction, yet our understanding of the signaling mechanisms controlling these processes in the heart remains incomplete. Understanding and preventing cardiomyocyte death and myocardial inflammation is an important strategy for reversing these adverse cardiac conditions and preserving myocardial function. Recent studies have revealed that innate immune system such as Toll-like receptor 4 (TLR4) signaling via MyD88 may play an important role in mediating tissue inflammation and regulating cell death/survival in response to non-infectious injury. Our investigation has focused on the role of TLR4 ® MyD88 signaling in modulating myocardial inflammatory injury and cardiac dysfunction after transient ischemia and to define the molecular and cellular mechanisms that govern these processes. This type of study could provide potential targets for intervention by modulating cardiac innate immune signaling pathway, either through tissue-specific gene transfer or pharmacological reagents.