Hyperhomocysteinemia Promotes The Expression Of Urotensin â…¡ And Its Receptor In The Development Of Restenosis After Abdominal Aortic Balloon Angioplasty In Rats

Background: Percutaneous Tranluminal Coronary Angioplasty ( PTCA ) and stent implantation are the very important interventional therapy in coronary artery disease. However, the restenosis is a severe complication for some patients after PTCA. The mechanisms of it have been not elucidated completely. It is reported that hyperhomocysteinemia can exacerbate the neointima formation in rat abdominal aorta after balloon injury. As a newly discovered vasoactive peptide, the function of urotensin II is unknown in the process of neointima formation after aorta injury. Our experiment is to study the expression of UII and the receptor of GPR14 in the neointima in hyperhomocysteinemia in rat abdominal aorta after balloon injury. As a result we can understand the role of the UII/GPR14 in hyperhomocysteinemia exacerbates neointima formation in rat abdominal aorta after balloon injury.Materials and methods: Forty Sprague Dawley male rats, about 200g body weigh, after a week of acclimatization, were randomly divided into four groups: the sham group (C), the high methionine supplement group(M), the abdominal aorta balloon injury(I), the high methionine supplement and abdominal aorta balloon injury group(MI). The M group and the MI group were fed the L-methionine (1g/kg/d) for four weeks and the C group and the I group only fed the normal feeds. After four weeks, the I group and the MI group were injuried the abdominal aorta with the balloon tube. The other two groups were only hypodesis the carotid artery.After the operation, the M group and the MI group continued to feed the high L-methionine (1g/kg/d)and the other two groups were continued the normal feeds for the other two weeks. At the end of the experiment, all rats were deprived of food overnight, anesthetized with pentobarbital, and killed. Plasma was stored at -80°C for analyzing the lever of the homocysteine and urotensin II. The abdominal aorta from each rats were then dissected into 2 segments:one for the HE staining and immunohistochemistry to observe the neointima and the expression of UII and GPR14, another for RT-PCR to determine the expression of GRP14 mRNA. Results were expressed as means±SD for each group of rats. One-way ANOVA and unpaired Student's t test were used to examine the differences among or between groups. Differences were considered significant at P<0.05.Results: Hyperhomocysteinemia was induced in rats by fed the high methionine diets. And it can exacerbate neointima formation in rat abdominal aorta in 14days after balloon injury. Immunohistochemistry found that the UII were little expressed in the intima and vascular smooth muscle cells in the C group and the M group,but high expressed in the neointima in the MI group and the I group, and the MI group was more higher expressed than the I group(P<0.01). GPR14 were both expressed in the intima and vascular smooth muscle cells in four groups,and the MI group was more higher expressed in the neointima than the I group(P<0.01). RT-PCR found that GPR14 mRNA were all expressed in four groups, MI group and I group were more higher expressed than the other two groups (P<0.01), also the MI group was higher than I group (P<0.05). But the UII lever in the blood plasma is not any difference(P>0.05).Conclusion:Hyperhomocysteinemia can exacerbate neointima formation in rat abdominal aorta after balloon injury. And it also promoted the expression of the UII and GPR14 in the neointima. The results suggested that the UII/GPR14 system may play a very important role in the pathogenesis of neointima formation in abdominal aorta of hyperhomocysteinemic rat after balloon injury.