| Background and purposeMyocardial ischemia is one of the leading causes of morbidity and mortality in humans in Western world. In China, the incidence and prevalence of this disease is also increasing year by year. Myocardial revascularization has been an established mainstay in the treatment of CAD for almost half a century. Coronary artery bypass grafting (CABG), used in clinical practice since the1960s, is arguably the most intensively studied surgical procedure ever undertaken, while percutaneous coronary intervention (PCI), used for over three decades, has been subjected to more randomized clinical trials (RCTs) than any other interventional procedure. PCI was first introduced in1977by Andreas Gruentzig and by the mid-1980s was promoted as an alternative to CABG. While both interventions have witnessed significant technological advances, in particular the use of drug-eluting stents (DES) in PCI and of arterial grafts in CABG, their role in the treatment of patients presenting with stable CAD is being challenged by advances in medical treatment, referred to as optimal medical therapy (OMT), which include intensive lifestyle and pharmacological management. Existing treatment, such as percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) are often insufficient, particularly in patients with multiple small vessel disease. Thus, there is clear need for the development of novel treatment approaches, such as therapeutic angiogenesis using protein or gene therapy. We were aware that angiogenic and angiostatic factors may work together to regulate angiogenesis. And the exact mechanism and relationship between them has not been clearly demonstrated. More research should be done to further explore the mechanism. We hypothesize that statin might significantly interfere with CD151in the angiogenic process. To address this important question, we used Atorvastatin, the most potent member of statin recently introduced as a powerful angiogenic agent for treatment of MI. And the exact mechanism and relationship between them was studied in a rat myocardial infarction model.Material and MethodsMale and female adult Sprague-Dawley rats (250-350g) were purchased from the Zhengzhou University Experimental Animal Center. We established the acute myocardial infarction rats model was by occlusion of the left anterior descending coronary artery. Among, the100rats used in our research,34died during the operation due to the severe MI, and6died by accident in6weeks.24hour after surgery,66rats were randomized to the model group, the sham operated group, and the Atorvastatin group. The rats were treated with normal saline in Control and Model Group; the rats were treated with Atorvastatin in Atorvastatin group for6weeks. The dose of Atorvastatin is10mg-kg-1·d-1.The rats were executed6weeks after treatment. Heart was harvested at6weeks post-MI. The heart was rapidly removed from killed rats. Sections from infarcted margion zone of each heart were stained by vWF staining. Capillary density was calculated as mean number of capillaries high power field(X400). CD151rnRNA was measured by reverse transcription-PCR. CD151protein was measured by Western bloting. All results were expressed as mean±tandard deviation.Differences between multiple groups were compared by analysis of variance (one-way ANOVA and LSD post test, SPSS18.0for Windows) where a value of P<0.05was considered statistically significant.ResultsRabbit anti-human factor Ⅷ-related antigen (vWF) polyclonal antibody immunohistochemical staining results show that the Atorvastatin group (3.99±0.52) of vWF staining positive microvessel counts have increased significantly compared with the model group (2.07±0.29). The model group (2.07±0.29) also increased significantly compared with the sham operated group (1.83±0.22). One-way ANOVA analysis showed that three groups difference was statistically significant (P <0.001). Pairwise comparisons analysis showed that the Atorvastatin group, the model group and the sham operated group were statistically significant (P=0.046<0.05). RT-PCR was used to detect the mRNA expression of CD151. The results indicated that the Atorvastatin group CD151mRNA expression levels (0.830±0.036) increased significantly compared with the model group (0.317±0.028) and the sham operated group (0.302±0.045). One-way ANOVA analysis showed that three groups were statistically significant difference (P<0.001). Pairwise comparison analysis showed that the Atorvastatin group and the model group, the sham operated group was statistically significant.There is no significant difference between the model group and the sham operated group (P>0.05). Western blot was used to detect the protein expression of CD151. The results indicated that the Atorvastatin intervention group CD151protein expression levels (0.410±0.025) increased significantly compared with the model group (0.148±0.013) and the sham operated group (0.139±0.009). One-way ANOVA analysis showed that three groups was statistically significant difference (P＜0.001). Pairwise comparison analysis showed that the Atorvastatin group and the model group, the sham operated group were statistically significant. The difference was not statistically significant (P=0.10>0.05) between the model group and the sham operated group.Conclusion1. Atorvastatin can enhance angiogenesis in ischemic myocardium.2. Atorvastatin can promote the mRNA and protein expression of CD151.3. We found that Atorvastatin promote ischemic myocardium angiogenesis by increasing CD151mRNA and CD151protein expression. |
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