Review Immune and Molecular Pathogenesis in Atherosclerosis

Atherosclerosis consists of focal lesions of the arterial intima characterized by cholesterol deposition, fibrosis and inflamation. Local endothelial expression of vascular cell adhesion molecule and chemotactis stimulation by oxidized LDL may be important for the formation in the early stage of the lesion. During the progression of the lesion, macrophages are transformed into lipid-laden foam a fibrous cap uptake of oxidized LDL, and smooth mucle cells migrate into the lesion to form a fibrous cap around the lipid-rich core. Activated macrophages and T lymphocytes may, by means of their cytokine secretion (interleukin 1, interleukin II, tumor necrosis factor-a, interferon-y, etc.), regulate genetic expression, foam cell formation, smooth muscle, cell proliferation, and the generation of free oxygen radicals. Cytokines promote angiogenesis, induce morphological and functional alterations in endothelial cells, cause expression of human leukocye antigen, stimulate cyclooxygenase activity and promote adhesion of polimorphonuclear cells on endothelial cells. Interferon-y down-regulates scavenger receptor expression and intracellular cholesterol accumulation; it also inhibits smooth muscle proliferation, collagen formation and induces nitric production. In conclusion, it is considered that the immune response in association with cytokines, in the atherosclerotic plaque plays an important and modulating role in the development of the disease. Further experiments will be necessary to determine the role of interleukin II antagonists, interferon-y, other cytokines and gene therapy in its regression and treatment.