Neuroimmunology of the atherosclerotic plaque: a morphological approach.

Atherosclerosis is a chronic inflammatory process, lasting for several decades until the onset of its clinical manifestations. The progression of the atherosclerotic lesion to a stable fibrotic plaque, narrowing the vascular lumen, or to a vulnerable plaque leading to main vascular complications, is associated to the involvement of several cell subpopulations of the innate as well as of the adaptive immunity, and to the release of chemokines and pro-inflammatory cytokines. Emerging evidence outlines that the cardiovascular risk is dependent on stress-mediators influencing cell migration and vascular remodeling. The view that atherosclerosis is initiated by monocytes and lymphocytes adhering to dysfunctional endothelial cells is substantiated by experimental and clinical observations. Macrophages, dendritic cells, T and B lymphocytes, granulocytes accumulating into the subendothelial space secrete and are stimulated by soluble factors, including peptides, proteases and cytokines acting synergistically. The final step of the disease, leading to plaque destabilization and rupture, is induced by the release, at the level of the fibrous cap, of metalloproteinases and elastases by the activated leukocytes which accumulate locally. Recruitment of specific cell subpopulations as well as the progression of atherosclerotic lesions towards a stable or an unstable phenotype, are related to the unbalance between pro-atherogenic and anti-atherogenic factors. In this connection stress hormones deserve particular attention, since their role in vascular remodeling, via vascular smooth cell proliferation, as well as in neoangiogenesis, via stimulation of endothelial cell proliferation and migration, has been already established.