Cellular and molecular players in the atherosclerotic plaque progression

Atherosclerosis initiation and progression is controlled by inflammatory molecular and cellular mediators. Cells of innate immunity, stimulated by various endogenous molecules that have undergone a transformation following an oxidative stress or nonenzymatic glycation processes, activate cells of the adaptive immunity, found at the borders of atheromas. In this way, an immune response against endogenous modified antigens takes place and gives rise to chronic low-level inflammation leading to the slow development of complex atherosclerotic plaques. These lesions will occasionally ulcerate, thus ending with fatal clinical events. Plaque macrophages represent the majority of leukocytes in the atherosclerotic lesions, and their secretory activity, including proinflammatory cytokines and matrix-degrading proteases, may be related to the fragilization of the fibrous cap and then to the rupture of the plaque. A considerable amount of work is currently focused on the identification of locally released proinflammatory factors that influence the evolution of the plaque to an unstable phenotype. A better understanding of these molecular processes may contribute to new treatment strategies. Mediators released by the immune system and associated with the development of carotid atherosclerosis are discussed.