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 proliferative process is controlled in part by the action of specific peptide growth factors that may influence early cell-cycle regulatory gene expression. Such ''early'' response genes include the protooncogene c-myc,, which has been implicated in the induction of cell proliferation and differentiation. We compared the distribution of the c-myc protooncogene product in healthy and atherosclerotic human carotid arteries to determine its cellular and tissue localization. Methods: Samples of six carotid artery plaques from six patients were rapidly frozen in liquid 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 polyclonal rabbit anti-c-myc antibody that recognizes the 64 kd c-myc human protein. The percentages of cells positive for c-myc (c-myc index) and the intensity of antibody labeling were determined. Results: Normal human carotid artery demonstrated minimal, isolated cell staining, with single scattered grains of immunocytochemical staining product seen in SMC nuclei. The myc index was 14.7% +/- 3.5% positive cells. In comparison, SMCs from carotid plaque showed a significant predominance of c-myc immunoreactive cells (89.8% +/-4%; p < 0.00 1). The intensity of c-myc staining was greater in plaque SMCs, with many of the cells demonstrating confluence of immunocytochemical precipitate throughout 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 and humoral factors may initiate the atherogenic process. The c-myc gene and other protooncogenes are early molecular markers of cell-cycle activity, which may be important in the development of atherosclerosis and occlusive vascular disease.