Morphological fate and sequelae of human atherosclerosis: Evaluation of immune mechanisms in atherogenesis through immunohistological and ultrastructural analysis

Abstract

Modern techniques of investigation have revealed several similarities between atherosclerosis and chronic inflammation, and that immune mechanisms seem to operate in the incipient and subsequent phases of atherosclerosis. In the present study, the fate and morphogenesis of human atherosclerosis was considered, and the immune aspects of atherogenesis were analysed, using fresh human aorta obtained from autopsy cases. One of the earliest changes in the grossly normal, lesion-prone area of the aorta from young cases (prelesional changes) was the infiltration of blood-borne T lymphocytes and monocytes/macrophages beneath the endothelium. Cell-populated lesions abounding in T lymphocytes and macrophages, often bearing signs of activation, with or without cytoplasmic lipids were found in the fatty streaks, cap and shoulder regions of more advanced atheromatous plaques. The ultrastructural observation of cell-rich areas suggested that cognate cell-to-cell interaction plays a pivotal role in atherosclerosis, as well as cytokine-mediated paracrine or autocrine mechanisms. From an immunological perspective, the areas where both cell types are especially numerous and in close proximity are considered to be the areas with an index of disease activeness or progressiveness. Also, the present authors show evidence of clonal expansion of T lymphocytes. It is most likely that the increase of intimal cells was caused by the recruitment of immunocompetent cells from the blood-stream into the intima and by the clonal expansion of T lymphocytes. In addition, dead or dying cells were identified in areas of different stages ranging from prelesional areas to atheromatous plaques. Thus, the initiation and progression of human atherosclerosis appears to be punctuated by brief episodes of immunological events related to cell infiltration, proliferation and death.