Effect And Mechnisms Of Connexin 43 In Low Shear Stress Induced Carotid Remodeling In Mice

Vascular remodeling defines as a progress in which the vessel morphology and function accommodate the environment during the period of growth, development, aging and diseases. Normal shear stress maintains vascular homeostasis while the pathological vascular remodeling would occur under low shear stress (LowSS), which could induce atherosclerosis, hypertension and restenosis. In this process, connexin (Cx) family plays important roles in direct communication between homologous and heterogeneous vascular cells. And they also have close relationship with growth, apoptosis, migration and inflammation of different types of vascular cells. Therefore, it is very important to elucidate expression and regulation mechanism of Cx in vascular remodeling induced by LowSS for prevention, diagnosis and treatment of cardiovascular diseases.In the present study, we ligated right external and internal carotid arteries to create low blood flow mouse model first. Sham-operated animals without ligation were serviced as a control group. The HE staining vascular sections were used to measure vascular morphology. The expressions of Cx43 and miR-206 in the vascular tissue were examined by Western blotting and Real-time PCR respectively. PDGF-BB (25 ng/ml) was added to cultured VSMCs in order to simulate LowSS stimulation in vitro, after which VSMC migration was examined by Transwell assay and the expressions of Cx43 and miR-206 were also demonstrated. MiR-206 siRNA was then used to deactivate miR-206 in VSMCs to elucidate whether miR-206 plays a role in regulating PDGF-BB induced VSMC migration and Cx43 expression. Cx43 siRNA was also used to find out correlation of Cx43 and PDGF-BB induced VSMC migration.The results showed that LowSS could induce a significant increase of ratio of wall thickness to inner diameter and of intima to media area. It also lead to neointimal formation, up-regulated expression of Cx43 and down-regulated expression of miR-206 in carotid artety. Recombinent PDGF-BB could significantly enhance VSMC migarition, up-regulate Cx43 expression and decrease miR-206 expression in VSMCs. miR-206 knockdown by siRNA treatment resulted in great increase in Cx43 expression and huge enhancement of VSMC migration induced by PDGF-BB. Whereas, Cx43 interference inhibited PDGF-BB induced VSMC migrationThe in vivo and in vitro results suggest that LowSS can induce pathological vascular remodeling of carotid artery with characteristic of neointimal formation. LowSS can regulate VSMC migration to attach itself to vascular remodeling in which Cx43 and miR-206 are both involved.