[Visualizing arterial macrophage warfare with nuclear magnetic resonance, positron-emission tomography and...

The macrophage is the principal immune cell found in atherosclerotic plaque. Although its function is to phagocytose foreign bodies present in the vascular endothelium, it can undergo a process of sustained activation that gives rise to a pattern of chronic inflammation, which may even trigger an acute coronary syndrome. The cellular response underlying this disease process is mediated by a complex molecular signaling cascade. Cytokines released by activated macrophages ultimately produce significant tissue damage by perpetuating the ongoing inflammatory response. Recent studies have shown that a defective interaction between the macrophage and its substrate could provide a mechanism for destabilizing atherosclerotic plaque by stimulating digestion of the artery and promoting plaque rupture. A key element in the life cycle of macrophages is that, when they cannot effectively remove the foreign bodies that have resulted in their activation, they initiate cell death (i.e., apoptosis), thereby releasing substances into the extracellular milieu that are even more toxic than inflammatory mediators. The significant advances in noninvasive molecular imaging techniques that have taken place in recent years have helped to unravel fundamental features of macrophage biology and have made it possible to explore the potential benefits of specific therapeutic interventions. Nanomarkers designed to home in on specific molecular targets have enabled imaging techniques to be used not only to study the pathophysiological mechanisms of atherosclerotic disease but also to diagnose such disease, and have made it possible to imagine the development of a form of nanomedicine based on administering treatment that can target a single cell type.