c-MYC oncoprotein production in experimental vein graft intimal hyperplasia.

PURPOSE

The expression of c-MYC oncoprotein in proliferating smooth muscle cells (SMCs) was analyzed in an experimental model of vein graft intimal thickening.

METHODS

Superficial epigastric vein grafts were inserted into the femoral arteries of male Sprague-Dawley rats. The vein grafts were harvested at 6 hr, 2 days, 1 week, 2 weeks, and 4 weeks after grafting and were rapidly frozen in liquid nitrogen. Immunohistochemical labeling and morphologic analysis of vein graft sections with a double staining technique were used to identify c-MYC/alpha SMC actin and proliferating cell nuclear antigen (PC10)/alpha SMC actin within intimal cells. c-MYC/alpha SMC actin and PC10/alpha SMC actin positive cells were quantitated in the perianastomotic area (R-1) and the body of the graft (R-2) for each time period. Total wall and intimal thickness of perfusion fixed vein grafts were measured with a computer digitized system.

RESULTS

Intimal and total wall thickening in the R-1 region peaked at 1 week (27.4 and 579.4 microns respectively) and were significantly thicker (P < 0.01) than the same region at 6 hr after graft implantation (6.0 and 113.5 microns respectively). Staining for c-MYC and PC10 in R-1 was also significantly higher (P < 0.05) at 1 week (5.75 and 7.00 positive cells/10 cells, respectively) compared with that at 6 hr (1.5 and 1.33, respectively). The R-1 region stabilized and remodeled over the following 3 weeks, while c-MYC and PC10 staining progressively decreased. In the R-2 region, intimal thickness significantly increased (P < 0.05) from 6 hr (4.0 micrometers) to 1 week (12.0 micrometers) and stabilized, while total wall thickness increased throughout the first week and the difference became significant at 2 weeks (P < 0.05). Staining for c-MYC and PC10 paralleled the staining in R-1 with a significant peak at 1 week (P < 0.05).

CONCLUSIONS

c-MYC oncoprotein is expressed early after experimental vein grafting, with peak expression at 1 week. This occurs during a period of maximal intimal thickening, SMC proliferation, and increased expression of PC10. Expression of c-myc protooncogene may contribute to the induction and regulation of SMC proliferation, producing intimal hyperplasia.