| Background and Objective Percutaneous transluminal coronary angioplasty (PTCA) is an important breakthrough of the therapy of cardio vascular disease, but vascular restenosis which has high incidence rate obviously influences the distant effect of PTCA. At present, studies consider the major mechanism of vascular restenosis refer to the elastic contraction of extended artery segment, migration and proliferation of vascular smooth muscle cell (VSMC), production of extracellular matrix, remoulding of vascular wall and participation and organization of thrombosis. The injury of endothelial cell leads to proliferation and migration of VSMC and subsequent neointimal hyperplasia, which confirmed an important pathologic pathogenesis of vascular restenosis after PTCA. It has recently been discovered that vascular remodeling also plays an important role in luminal loss after PTCA. Interrelationship of intimal hyperplasia with vascular remodeling and their role in luminal loss during forming of vascular restenosis has not been elucidated completely. The phenotypic modulation of VSMC from contractile phenotype to synthesis phenotype is the key initial step ofmigration and proliferation of VSMC, however, so far its mechanism of gene regulation has not been confirmed. We had recently discovered cellular repressor of ElA-stimulated genes (CREG), which may correlate with VSMC differentiation and regulation of phenotypic modulation by differential display polymerase chain reaction (PCR) with cloned VSMC HITASY derived from adult human internal thoracic artery. By far the effect with CREG in function of VSMC was not reported. In this study, we used the model of vascular restenosis established by balloon injury of rat carotid arteries and observed pathologic change of the arterial wall, and detected the change of proliferation cell nuclear antigen (PCNA) and smooth muscle a-actin (SM a-actin) expression of neointimal formation and CREG expression of the arterial wall at different time after balloon injury. The aims of this study are to determine the regularity of intimal hyperplasia and vascular remodeling and their interrelationship in order to explore their role in luminal loss during forming of vascular restenosis, and to confirme the regularity of proliferation and phenotypic modulation of VSMC and the regulation role of CREG during neointimal proliferation so as to contribute to prevention and therapy of vascular proliferative diseases by CREG.Methods (1) The model of vascular restenosis established by balloon injury of rat carotid arteries was performed. Rats were killed at different time after balloon injury. Sections of balloon injury were taken out and made specimens, and stained with HE. Pathologic change of the arterial wall at different time after balloon injury was observed by microscopy. (2) Lumen area, thickness and area of intima and media, and cross-sectional area bounded by the external elastic lamina (EEL) at different time after balloon injury were measured by computer image analysis technology. (3) Total RNA was prepared by the Trizol extraction from rat carotid arteries. Reverse transcriptase-PCR was used to measure the change of CREG mRNA expression of rat carotid arteries wall at different time after balloon injury. (4) Immunohistochemistry was used to detect the change of PCNA and SM a-actin and CREG protein expression of the arterial wall at different time afterballoon injury.Results (1) Vascular morphology changes: In normal rat carotid artery, endothelium is complete. Endothelial cells were denudated immediately after balloon injury. The proliferating of VSMC was spotted on the surface of lumen at 3 days after balloon injury. At 7 days after injury, the neointima was formed and continuously thickening. At 28 days after injury, thickness of the neointima was maximal, and extracellular matrix was increased obviously and vascular lumen was narrowed seriously. At 35 days after injury, thickness of neointima was significantly smaller than that at 28 days after injury (P < 0.01), but vascular lume...
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