Effects and mechanisms of hyperhomocysteinemia on intimal hyperplasia in balloon-injuried rats carotid arteries

Objective To study the effects and mechanisms of diet-induced hyperhomocysteinemia on intimal hyperplasia of balloon-injured carotid arteries in rats. Methods Wistar rats were bred with 1 g/(kg·d) L-methionine. After 4 weeks, all animals underwent left common carotid arteries balloon denudation and the left common carotid arteries was extracted at day 14 and 28. The areas of carotid arteries intima and media, the proliferative index of smooth muscle cell and the percentage of reendothelization were measured and calculated. Results Intimal hyperplasia developed in all balloon-injuried arteries. The neointimal hyperplasia in the HHCY group was more obvious than that of the control group. The intimal thickness, neointimal area, Intima/Media area ratio were increased by 36%, 41%, 36% at 14 day and 33%, 30%, 21% at 28 day, respectively. Luminal area was decreased markedly in HHCY group. The percentage of intimal and medial PCNA positive cells increased by 1.7-fold and 2.3-fold at 14day. The percentage of endothelial covering area was decreased by 52% at 14day and 31% at 28day in HHCY group. Conclusion Diet induced hyperhomocysteinemia can stimulate SMC proliferation and inhibit endothelial regeneration, which leads to exacerbated intimal hyperplasia. This study implicates that homocysteine may be a significant risk factor for restenosis following vascular intervention.