DISTRIBUTION OF C-MYC ONCOPROTEIN IN HEALTHY AND ATHEROSCLEROTIC HUMAN CAROTID ARTERIES

Purpose: Smooth muscle cell (SMC) proliferation is a central event in the development of arteriosclerotic plaque. Regulation of this prolife rative process is controlled in part by the action of specific peptide growth factors that may influence early cell-cycle regulatory gene ex pression. Such ''early'' response genes include the protooncogene c-my c,, which has been implicated in the induction of cell proliferation a nd differentiation. We compared the distribution of the c-myc protoonc ogene product in healthy and atherosclerotic human carotid arteries to determine its cellular and tissue localization. Methods: Samples of s ix carotid artery plaques from six patients were rapidly frozen in liq uid nitrogen at the time of carotid endarterectomy. Three nondiseased human carotid arteries obtained at organ harvest from brain-dead organ donors were similarly prepared. Frozen sections were labeled with a p olyclonal rabbit anti-c-myc antibody that recognizes the 64 kd c-myc h uman protein. The percentages of cells positive for c-myc (c-myc index ) and the intensity of antibody labeling were determined. Results: Nor mal human carotid artery demonstrated minimal, isolated cell staining, with single scattered grains of immunocytochemical staining product s een in SMC nuclei. The myc index was 14.7% +/- 3.5% positive cells. In comparison, SMCs from carotid plaque showed a significant predominanc e of c-myc immunoreactive cells (89.8% +/-4%; p < 0.00 1). The intensi ty of c-myc staining was greater in plaque SMCs, with many of the cell s demonstrating confluence of immunocytochemical precipitate throughou t 50% of SMC nuclei. Conclusions: Although the exact role of enhanced expression of the c-myc protooncogene in atherosclerosis is unclear, a cooperative influence of abnormal early cell-cycle gene expression an d humoral factors may initiate the atherogenic process. The c-myc gene and other protooncogenes are early molecular markers of cell-cycle ac tivity, which may be important in the development of atherosclerosis a nd occlusive vascular disease.