Targeting the chemokines in myocardial inflammation.

Abstract

The chemokines comprise a large family of small, highly basic proteins that play a critical role in basal and inflammatory leukocyte locomotion and trafficking.1,2 In addition to effects on cell locomotion, certain chemokines are capable of eliciting a variety of other responses affecting leukocyte adhesion, activation, and degranulation, mitogenesis, and apoptosis. Furthermore, chemokines have a wide range of effects on many different cell types beyond the immune system, including endothelial cells, fibroblasts, smooth muscle cells, neurons, and epithelial cells. See p 1443 Involvement of chemokines in the pathobiology of conditions such as multiple sclerosis, HIV disease, asthma, rheumatoid arthritis, atherosclerosis, and neoplasia has been inferred by animal model experiments and supported by correlative data in humans. Although recent investigations indicated marked chemokine upregulation in the myocardial inflammatory processes associated with infarction,3–5 ischemic cardiomyopathy,6,7 allograft rejection,8,9 and myocarditis, the exact role of chemokine signaling in myocardial pathology remains poorly understood. Chemokine induction seems to be a prominent response to myocardial injury in a variety of situations. In myocardial infarcts, cellular necrosis may trigger several chemokine-inducing pathways regulated through free radical generation, nuclear factor-κB activation, tumor necrosis …