| Objective: Migration and proliferation of smooth muscle cells (SMC),andsynthesis of extracellular matrix by these cells, are key events underlying atherosclerotic disease and the healing response to vascular injury following balloon angioplasty, stent implantation, and atherectomy. Although the precise pathogenetic features of these processes differ in specific detail, all involve transformation of SMCs from the differentiated contractile state to the activated synthetic state. Gap junctions comprise clusters of transmembrane channels that act as conduits for the direct intercellular exchange of ions, secondary messengers, and small signaling molecules, a key function to tissue homeostasis and the regulation of growth, differentiation, and development. Connexins are the component proteins of gap junctions. Upregulation of connexin43 gap junction between SMCs is a conspicuous early event in the development of atherosclerotic lesions and healing response to vascular injury. HMG-CoA reductase inhibitors can dose-dependently inhibit Cx43 expression in culture SMCs of human origin. This study was designed to investigate whether there is connexin40 expression between SMCs of rabbit arterial wall and how connexin40 expression changes in proliferating SMCs induced by balloon injury or atherosclerosis, Whether HMG-CoA reductase inhibitors can inhibit Cx43and Cx40 expression in proliferating SMCs induced by balloon injury or atherosclerosis. Is there different in the effect on connexin during the process between the hydrophilic pravastatin and lipophilic fluvastatin.Methods: 1. Establishing models of rabbit with balloon catheter injury: forty-two adult male New Zealand White rabbits were divedided into 6 groups: normal control group, sham operation group, balloon injure group, balloon injury + lovastatin group, balloon injury + fluvastatin group, balloon injury + pravastatin group. Animals were sacrificed 2 weeks after balloon injury. Iliac arteries were dissected. 2. Establishing models of rabbit with high-cholesterol diet: thirty-five adult male New Zealand White rabbits were divedided into 5 groups: normal control group, high-cholesterol diet group, high-cholesterol diet + lovastatin group, high-cholesterol diet + fluvastatin group, high-cholesterol diet + pravastatin group. Except normal control group, all rabbits were fed normal diet after high-cholesterol diet for 6 weeks, and received drugs at 10 mg/kg/d in their diet at the same time. 2 weeks later, all animals were sacrificed. Abdominal aorta were dissected. 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). Theprotein and mRNA expression of Cx43 and Cx40 between SMCs was markedly upregulated after balloon catheter injury (P<0. 001). Lovastatin, fluvastatin and pravastatin can reduce the protein and mRNA expression of Cx43 and Cx40, but the levels were higher than those of the undiseased vessel. There was no difference in protein and mRNA expression of Cx43 and Cx40 between the groups treated by Lovastatin, fluvastatin and pravastatin respectively. Immunolabeled connexin40 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 and Cx40 gap junction labeling in the neointima zone was declined, but was higher than normal...
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