Biology of the smooth muscle cells in human atherosclerosis

The aim of this study was to reconstruct dynamic biological steps of human atherosclerosis at different ages of life and, in particular, to clarify the role of the smooth muscle cells (SMCs) by means of evaluation of several markers implicated in proliferative diseases (c-fos, proliferating cell nuclear antigen: PCNA, apoptosis, chromosome 7). We examined the biological features of 67 atherosclerotic arterial lesions obtained from fetuses, infants, young people and adults. From each case serial sections were stained for histological examination, PCNA, c-fos and apoptosis detection by immunohistochemical methods and for chromosome 7 number evaluation by fluorescence in situ hybridization. In coronary specimens of fetuses we observed SMCs with c-fos positivity. In infant lesions the predominant result was positivity for PCNA. Similar results were obtained from the plaques from young subjects with a greater presence of PCNA-positive cells. In adult subjects numerous apoptotic cells were present in the stable plaques, whereas in the unstable plaques we frequently detected joint positivity for both PCNA and c-fos gene and supernumerary chromosomes 7. During the evolution of the atherosclerotic process we observed a biological modulation of SMC proliferation, which begins after activation of the c-fos gene, increases during progression of the lesion and declines in stable plaques, when apoptosis increases. In unstable plaques, the same early steps observed in fetus and infant arteries occur. The observation in some cases of chromosome 7 alterations, markers of tumorigenesis, suggests the possible transformation of an advanced atherosclerotic plaque into a neoplastic-like process.