Mast cells in atherogenesis: Actions and reactions

Abstract

Mast cells (better known as allergy cells) are proinflammatory effector cells present in the human arterial intima and in evolving atherosclerotic lesions. Experiments in vitro, in vivo experiments in animals, and immunohistologic studies of human coronary samples have uncovered mechanisms by which activated mast cells could participate in the development of the lesions. When activated, mast cells acutely expel a fraction of their cytoplasmic granules, which are filled with a wide selection of heparin-bound preformed mediators. These include histamine, neutral proteases, growth factors, and proinflammatory cytokines. The microenvironmental targets of these effector molecules are various lipoprotein particles in the intimal fluid, components of the extracellular matrix, and intimal cells neighboring the activated mast cells. Importantly, sustained selective release of proinflammatory mediators without degranulation may also occur at sites of chronic inflammation. The activities of the various mediators are suggested to contribute to fatty streak formation and to the generation of unstable plaques susceptible to rupture. Thus, mast cells appear to provide a novel link between inflammation and atherogenesis.