The Effect Of Connexin 43 Remolding In Vascular Restenosis

Background: The long-dated therapeutic effect of percutaneous coronary intervention (PCI) is compromised by the high incidence of post-angioplasty restenosis which has not been solved yet. To explore the pathogenesis and find new therapy of RS is currently a hot subject and difficult point in research area of cardiovascular pharmacology. Some studies demonstrate that gap junction (GJ) takes part in the process of vascular smooth muscle cells (VSMCs) migration and proliferation. Increasing evidence shows that Cx43 gap junction remodeling under many pathological conditions can significantly affect the function of blood vessels.Objective: To investigate the role of GJ in the pathogenesis of RS, we examined Cx43 expression and analyzed the relationship between Cx43 expression and different phases in development of neointima formation after balloon catheter injury in hyperlipemia rats, which will provide experimental basis for the treatment of RS.Methods: Twenty-five adult Sprague-Dawley rats were randomly assigned into five groups(n=5). The control group consumed regular chew for 8 weeks before right common carotid arteries were taken out directly; and the other four groups were exposed to an atherogenic diet for 8 weeks before balloon distension injury in the common carotid arteries. Peripheral blood was collected for analysis of plasma total cholesterol (TC) and triglyceride (TG) levels. Body weight was also measured before and after 8 weeks. According to the samples taken at different times after injury, rats were sacrificed 0d, 7d, 14d and 28d, respectively. All artery speciments were performed for morphometric analysis, including hematoxylin-eosin (HE) staining and immunohistochemistry, semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and western Blotting studies, respectively.Results: Both body weight and plasma levels of TG and TC were significantly increased after 8 weeks with an atherogenic diet in rats(P<0.01).After HE staining, intact endothelial layer was observed in normal carotid arteries, and the long spindle-shaped VSMCs in the media layer were well arranged. At 0 day after injury , the endothelial cells were virtually absent. 7 days after injury, low-grade neointima began to form at local lumen, with a lot of inflammatory cells infiltration. To 14 days, VSMCs proliferation was markedly increased. Disorders of VSMCs were observed in neointima with a growth tendency toward luminal surface. At 28 days, lumen size was dramatically decreased, and the shape of some VSMCs in neointima was quite close to those in media.Immunohistochemistry of Cx43 showed a characteristic pattern in the form of scattered, sharply defined punctuate staining throughout the media in five groups. Moreover, a significantly strong immunostaining of Cx43 labeling was found in the new-formed neointima zone, especially in 28 days group after injury.RT-PCR and Western Blotting were used to detect Cx43 mRNA and protein expression, respectively. Results showed that Cx43 mRNA and protein expression were declined 7d after injury compared with 0d group(P<0.01); and they were markedly upregulated with the progress of RS, especially in 28 days group.Conclusions:â‘ Histology and immunohistochemistry show that arteries become re-narrowed after balloon catheter injury in rats with an atherogenic diet.â‘¡Both Cx43 mRNA and protein expression are declined at early stage, and subsequently increased during vascular restenosis induced by the new formation of neointima after balloon catheter injury in rats.â‘¢The remodeling of Cx43 may be involved in the development of RS after PCI, which will provide a new therapeutic basis for RS.