The Effect Of Simvastatin On Expression Of α-Smooth Muscle Actin After Stenting In Abdominal Aorta Of Rabbits

Background and Objective: Percutaneous coronary intervention (PCI) is a very important technology for the treatment of patients with coronary heart disease. However, the problem is that restenosis after percutaneous transluminal coronary angioplasty (PTCA) occurs about 30% to 40% of all of the patients. The advent of stenting has resulted in a significant (30% to 50%) decrease of restenosis rate. However , in-stent restenosis (ISR) represents a major limitation of this procedure (PCI) .The mechanisms responsible for restenosis after balloon angioplasty are mainly the negative remodeling of vessel that accounts for 75% of the phenomenon and the proliferation of smooth muscle cell (SMC) with neointima formation that represents the other 25%. ISR is 100% due to SMC proliferation , remodeling of the vessel does not occur.Statins are powerful low-density lipoprotein lowering drugs that are widely used in clinical practice in the setting of either primary or secondary prevention. Recent evidents indicated that some of the cholesterol-independent or pleiotropic effect of statins involve inhibiting proliferation migration of SMC and inducing apoptosis of SMC, especially simvastatin more powerful. So, in order to acquire more knowledge on mechanism of ISR, rabbits underwent abdominalaorta balloon de-endothelialization and were treated with a 1.5% cholesterol diet .Then stenting was performed on the stenosis to induce the formation of neointima . The stenting-rabbits were orally administered with simvastatin (5mg/d) . The effect of simvastatin on the expression of a -SM actin was investigated and compared with the control group. Methods Fifteen male New Zealand white rabbits were studied. The rabbits were fed on normal diet (normal group n=5), or a cholesterol diet (1.5%)(n=10, contrlo group n=5, treating group n=5, respectively. ). Cholesterol fed rabbits underwent balloon injury of abdominal aorta under sterile conditions from femoral approach. Ultrasonographic image and angiography on abdominal aorta were performed in 10th weeks to measure the degree of stenosis. Treating group was administered simvastatin (5mg/d) once the stenosis is formed. Three days before stenting, these rabbits were also administered with aspirin and clopidogrel . Three days later, stents were implanted on the segment of stenosis (>50%). Rabbits were killed 30 days after stenting and stented abdominal aorta was harvested . The neointima and the underlying media were seperated from the stent .The whole wall arteries underwent protein extraction, electrophoresis and Western blot .Expression of a ?SM actin of contractile phenotype SMC was measured in 3 groups.Results In 10th weeks .atherosclerosis and stenosis of abdominal aorta were observed by ultrasonographic images and the degree of stenosis was 53.97016.136% after balloon denudation .Angiography on abdominal aorta demonstrated that the degree of stenosis was 57.00017.888% (P> 0.05) .Reference lumen diameter was 2. 88810.052mm in ultrasonographic image and 2.955 + 0. 117mm (P>0.05) in angiography. Minimum lumen diameter was 1. 57310. 191mm in ultrasonographic image and 1. 680 + 0. 199mm in angiography ( P > 0.05 ) . It was not significant difference statistically .So dopper ultrasonography appears suitable for measuringstenosis of the abdominal aorta when compared to angiography . (2) Western blot results were as follows: the expression of a ?SM actin in control group without simvastatin decreased significantly (55.4%) compared with normal group. In simvastatin group the expression of a ?SM actin decreased 28.7% compared with control group. The relative value of a ?SM act in in 3 groups were: 1?, 0.446 ?.050, 0.314 ?.017 (P<0.05). respectively.Conclusion (1) Model-making of atherosclerosis and stenosis is feasible by balloon denudation plus cholesterol-supplemented diet (1. 5%) with rabbits from femoral approach. (2) Doppler ultrasonography appear suitable for measuring stenosis degree of the abdominal aorta when compared to angiography. (3) The results of Western blot demon...