Davis Joseph A, Brown Aliza T, Chen Hongjiang, Wang Yunfang, Poirier Lionel A, Eidt John F, Cruz Carlos P, Moursi Mohammed M
University of Arkansas for Medical Sciences, Central Arkansas Veterans HealthCare System, 4300 West 7th Street, Little Rock, AR 72205, USA.
J Surg Res. 2004 Sep;121(1):69-75. doi: 10.1016/j.jss.2004.04.001.
Homocysteine and smoking are independent risks for CVD; however their importance in post-CEA intimal hyperplasia is unclear. We performed a CEA in rats exposed to cigarette smoke with the hypothesis that smoking would increase intimal hyperplasia that may be associated with an elevated serum homocysteine. Folic acid (FA) and the homocysteine metabolic enzymes MTHFR and CBS were used to test for the significance of homocysteine elevation.
Rats underwent an open CEA. N = 13 rats received smoke exposure 2 weeks prior, and 2 weeks post-CEA and N = 12 received no smoke. Each group was divided into either control or an FA-added diet resulting in four groups. Rats were sacrificed at 2 weeks post-CEA; liver, urine, blood, and carotid arteries samples were obtained.
Smoked rats had increased urinary peak and trough cotinine levels versus non-smoke rats, which decreased with FA. Smoke exposure increased intimal hyperplasia versus non-smoke controls by nearly 120% (57.8 +/- 6.2 versus 26.8 +/- 5.4% luminal stenosis, P = 0.005). Smoke-exposed rats had an increased serum homocysteine versus non-smoke controls (8.3 +/- 0.8 versus 5.7 +/- 0.8 microm, P = 0.014). Smoked rats given FA had decreased serum homocysteine compared to the smoke group. Along with reductions in homocysteine, FA eliminated the increase in intimal hyperplasia seen with smoke exposure (33.5 +/- 6.1 versus 57.8 +/- 6.2% luminal stenosis, P = 0.03). CBS activity decreased in smoked rats by nearly 20% versus non-smoke rats. FA supplementation in smoked rats both (1) increased CBS activity and (2) decreased MTHFR compared to control non-smoke-exposure levels.
Smoking increases plasma homocysteine and post-CEA intimal hyperplasia. This suggests homocysteine has an etiological role in the intimal hyperplasia increase observed with smoking, since both were negated with FA.
同型半胱氨酸和吸烟是心血管疾病（CVD）的独立风险因素；然而，它们在颈动脉内膜切除术后内膜增生中的重要性尚不清楚。我们对暴露于香烟烟雾的大鼠进行了颈动脉内膜切除术，假设吸烟会增加内膜增生，这可能与血清同型半胱氨酸升高有关。使用叶酸（FA）以及同型半胱氨酸代谢酶亚甲基四氢叶酸还原酶（MTHFR）和胱硫醚-β-合成酶（CBS）来检测同型半胱氨酸升高的意义。
大鼠接受开放性颈动脉内膜切除术。13只大鼠在颈动脉内膜切除术前2周和术后2周接受烟雾暴露，12只大鼠未接受烟雾暴露。每组再分为对照组或添加叶酸的饮食组，共形成四组。大鼠在颈动脉内膜切除术后2周处死；获取肝脏、尿液、血液和颈动脉样本。
与未吸烟大鼠相比，吸烟大鼠尿液中可替宁的峰值和谷值水平升高，而添加叶酸后降低。与未吸烟对照组相比，烟雾暴露使内膜增生增加了近120%（管腔狭窄率分别为57.8±6.2%和26.8±5.4%，P = 0.005）。与未吸烟对照组相比，暴露于烟雾的大鼠血清同型半胱氨酸升高（分别为8.3±0.8和5.7±0.8微摩尔，P = 0.014）。与烟雾组相比，给予叶酸的吸烟大鼠血清同型半胱氨酸降低。随着同型半胱氨酸的降低，叶酸消除了烟雾暴露引起的内膜增生增加（管腔狭窄率分别为33.5±6.1%和57.8±6.2%，P = 0.03）。与未吸烟大鼠相比，吸烟大鼠的CBS活性降低了近20%。与未暴露于烟雾的对照组相比，吸烟大鼠补充叶酸后，（1）CBS活性增加，（2）MTHFR降低。
吸烟会增加血浆同型半胱氨酸水平以及颈动脉内膜切除术后的内膜增生。这表明同型半胱氨酸在吸烟引起的内膜增生增加中具有病因学作用，因为两者都可被叶酸消除。
