| Objective: The migration and proliferation of vascular smooth muscle cells(VSMCs) is the common pathologic character of hypertension, atherosclerosis, angioplasty, especially percutaneous transluminal coronary angioplasty (PTCA), et al, cardiovascular diseases. The signals transfer from extracells into nucleus of cells at the all kinds of stimulations outsides and induce the expression of the genes correlation with the proliferation of VSMC, then startup cycles of the cells, drive migration and proliferation of VSMC. Gap junctions and Connexins play the important roles during the process. At present, three connexins, Cx43, Cx40, and Cx37, have been found by protein or mRNA analysis in mammalian blood vessels. Upregulation of connexin43 gap junction between VSMCs is a conspicuous early event in the development of atherosclerotic lesions and healing response to vascular injury. Angiotensin II(Ang II) stimulated the expression of connexin43 of the cardiac muscle cells incubated have been studied. This study was designed to investigate whether there is connexin40 and connexin43 expression changes between VSMCs of rabbit arterial wall in proliferating VSMCs induced by balloon injury or atherosclerosis, Whether angiotensin-converting enzyme inhibitor(ACEl) andAngiotensin II Type 1 Receptor(AT1R) inhibitors can inhibit Cx43 and Cx40 expression in proliferating SMCs induced by balloon injury or atherosclerosis.Methods:1. Establishing models of rabbit with balloon catheter injury: thirty-five adult male New Zealand White rabbits were divedided into 5 groups: normal control group, sham operation group, balloon injure group, balloon injury + losartan group, balloon injury + amipril group, Except normal control group, all rabbits received losartan at 10 mg/kg/d and ramipril at 0.5 mg/kg/d in their diet at the same time. Animals were sacrificed 2 weeks after balloon injury. Iliac arteries were dissected.2. Establishing models of rabbit with high-cholesterol diet: twenty-eight adult male New Zealand White rabbits were divedided into 5 groups: normal control group, high-cholesterol diet group, high-cholesterol diet + ramipril group, high-cholesterol diet + losartan group. Except normal control group, all rabbits were fed high-cholesterol diet for 8 weeks, and received Losartan at 10 mg/kg/d and ramipril at 0.5 mg/kg/d in their diet at the same time. 8 weeks later, all animals were sacrificed. Abdominal aorta were dissected.3 All specimens were immediately fixed for immunohistochemistry and electron microscopy. The others were harvested for Western blot, and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) studies respectively.Results:1. Rabbit with balloon catheter injury models: The presence of mRNA encoding Cx40 and Cx40 protein were detected in the rabbit iliac artery by reverse transcription-polymerase chain reaction and western blot. There was no difference in protein and mRNA expression of Cx43 and Cx40 between normal control group and sham operation group (P>0.05). The protein and mRNA expression of Cx43 and Cx40between SMCs was markedly upregulated after balloon catheter injury(P<0.01). Losartan and ramipril can reduce the protein and mRNA expression of Cx43(P<0.05 or P<0.01), but can not reduce the protein and mRNA expression of Cx40. There was no difference in protein and mRNA expression of Cx43 and Cx40 between the groups treated by losartan and ramipril respectively. Immunolabeled connexin40 and connexin43 gap junctions in control(noninjured) arteries showed a characteristic pattern in the form of scattered, sharply defined spots throughout the media. A significantly higher concentration of Cx43 and Cx40 gap junction labeling was apparent in the neointima zone of injured arteries than negative controls. After treatment with statins, the concentration of Cx43 gap junction labeling in the neointima zone was declined, but was higher than normal. There no changes of Cx40 expression. Electron microscopy revealed aboudant gap junction between neointimal VSMCs and fewer, smaller gap junctions betwee... |
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