Biomarkers of Ischemia in Patients With Known Coronary Artery Disease
Do Interleukin-6 and Tissue Factor Measurements During Dobutamine Stress Echocardiography Give Additional Insight?
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A fundamental understanding of the mediators and mechanisms associated with the pathophysiological process of reversible myocardial ischemic injury would be a substantial advancement in our basic understanding of this process and would speed the translation from “bench to bedside.” For example, elucidation of the chemical signals that both indicate the presence and extent of reversible ischemia and have a putative role in cellular dysfunction and injury would clearly have potential as a valuable biomarker for the development of diagnostic tools, in the clinical management of patients, and perhaps as a guide for the development of viable therapeutic targets. Focusing on the inflammatory process would seem to have a high likelihood for success because ischemic events, infection, and mechanical cell injury are known to activate numerous pluripotent pathways, cascades, and networks, including the cytokine and coagulation systems. These systems are highly integrated and redundant because of their critical role in the survival of the organism. Inflammatory cytokines such as interleukin-6 (IL-6) are low-molecular-weight pluripotent glycoproteins with a dynamic range of local and systemic actions and a wide range of target cells and organs.1 In many instances, individual cytokines have multiple biological activities that confer functional redundancy during inflammation and tissue repair; different cytokines can also have the same activity. Inflammatory cytokines and cytokine networks are also intimately associated with other injury response systems, including the coagulation system that controls for fibrinogenesis and fibrinolysis, with all its associated matrices, proteases, and metabolites, including fibrin, thrombin, plasmin, fibrinopeptides, and fibrin metabolites, to name a few. Central to the coagulation system is the transmembrane glycoprotein known as tissue factor, which controls clot formation via the extrinsic pathway. The coordinated integration of cytokine networks and coagulation cascades is essential in controlling inflammation and repair. For example, cytokines such as IL-1, tissue necrosis factor, and …