Alden H. Harken

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BACKGROUND The heart is a tumor necrosis factor-alpha (TNF-alpha)-producing organ. Recent basic experimental and clinical evidence suggests that TNF-alpha is an important mediator of myocardial injury during acute myocardial infarction, chronic heart failure, cardiac allograft rejection, and cardiopulmonary bypass operations. Although it is known that the(More)
Preconditioning may find ready applicability in humans facing scheduled global cardiac ischemia-reperfusion (IR) during bypass or transplantation, where such a maneuver is feasible before arrest. Our objective was to delineate and exploit the endogenous preconditioning mechanism triggered by transient ischemia (TI) and thereby attenuate myocardial(More)
Toll-like receptor 4 (TLR-4), initially identified as an LPS receptor, is critical to the signaling of a variety of danger signals, including heat shock protein 60, fibrinogen, and fibronectin. Recent data also suggest that TLR-4 plays a role in determining survival in both endotoxemia and hemorrhagic shock. We hypothesized that a functional TLR-4 would be(More)
Trauma induces many dramatic and complex changes in host cellular response. This complexity arises from the constellation of signals induced by stress, infection, and injury. Cellular priming, defined as altered response to an agonist induced by an antecedent stimulus, appears to be operative after trauma. If the interaction between two signalling pathways(More)
Atherosclerosis represents a spectrum of pathologic lesions with diverse clinical sequelae. In this review, we build upon the paradigm that arteriosclerosis represents an inflammatory disease. By examining mechanisms involved in the response to vascular injury, we can more effectively implement targeted therapy aimed at halting or regressing(More)
Background. Vessel injury results in an inflammatory response characterized by the elaboration of cytokines and growth factors, which ultimately influence vascular smooth muscle cell (VSMC) growth and contribute to atherogenesis. Nuclear factor-kappa B (NF␬B) is a central transcription factor important in mediating stress and inflammatory-induced signals.(More)
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