Mast Cells as Mediators and Modulators of Atherogenesis

he central role of inflammation in atherogenesis has gained broad acceptance and has revolutionized our understanding of this common disease. This recognition has heightened interest in identifying the specific mediators and mechanisms that contribute to the interplay between risk factors (traditional and emerging), inflammation, and the altered biol- ogy of the arterial wall that regulates plaque development and complication.1 In particular, leukocytes have come to occupy center stage as the major cellular effectors of inflammation. When these inflammatory cells join endothelial and smooth- muscle cells in the artery wall, they spur much of the biology that drives atherogenesis and plaque complication. Article p 2516 The list of leukocyte subtypes involved in arterial inflammation has entered a flourishing phase of refinement. Our understanding of leukocyte involvement in atherogenesis has gone through several strata of discovery and probing. During the initial descriptive phase, the use of rigorous molecular markers buttressed venerable mor- phological observations and verified the presence of various leuko- cyte classes within lesions.2 Later, a phase of experimental valida- tion established the causal relationship between leukocyte accumulation in lesions and the aspects of atherogenesis.3-5 Next, continuing mechanistic exploration has probed the precise molecu- lar pathways by which a given leukocyte population can promote or otherwise modify disease.6 Ultimately, the human relevance of in vitro and animal experiments requires observations in human tissues and in patients.