HYPERHOMOCYSTEINEMIA INCREASES INTIMAL HYPERPLASIA IN A RAT CAROTID ENDARTERECTOMY MODEL

Purpose: This preliminary study investigated the ability to elevate th e serum homocysteine (H[e]) levels and investigated the increases in p ostoperative neointimal hyperplasia (IH) in an environment with hyperh omocysteinemia and the resultant restenosis in a rat carotid endartere ctomy (CEA) model. Method: The 9 rats for the control group were fed r at chow, and the 8 rats for the H(e) group were fed H(e)-supplemented rat chow for 2 weeks before and after CEA. The animals underwent anest hesia, and a left common CEA was performed. After 14 days, the serum H (e) levels were measured and the left carotid artery was harvested and elastin stained. Morphometric measurements were used to calculate the area of stenosis of the lumen. The mean and the standard deviation of the mean were determined. The 2 groups were compared with the Mann-Wh itney test and a linear regression model. Three additional rats per gr oup were studied, with carotid artery sectioning with double immunohis tochemical staining for 5-bromodeoxyuridine (BrdU) and alpha-smooth mu scle (alpha-SM) actin. Results: The serum H(e) level in the H(e) group was 36.32 mu mol/L +/- 15.28, and in the control group the level was 5.53 mu mol/L +/- 2.06 (P = .0007). IH presented as percent lumen sten osis was 21.89% +/- 4.82% in the H(e) group and 4.82% +/- 1.64% in the control group (P = .0007). The linear regression model of the serum H (e) levels and the percent stenosis showed a linear relationship (r(2) = .72). The alpha-SM actin staining revealed that nearly all of the c ells in the IH area were of smooth muscle or myofibroblast origin and that 10.1% +/- 2.6% of the cells were-stained for BrdU in the control group versus 23% +/- 7.1% in the H(e) group. Also, 9.3% +/- 2.6% of th e cells in the IH area were stained for BrdU and for alpha-SM actin ve rsus 19.1% +/- 5.6% stained for both BrdU and alpha-SM actin in the H( e) group. Conclusion: This is the first study to examine IH after CEA and hyperhomocysteinemia in rats. The study shows that the elevation o f serum H(e) levels can be obtained by feeding rats modified diets wit h added H(e). The consistent elevation of serum H(e) levels was associ ated with more than 4 times the amount of IH after a CEA in a rat mode l.