Knockdown of connexin 43 attenuates balloon injury-induced vascular restenosis through the inhibition of the proliferation and migration of vascular smooth muscle cells

摘要

Coronary artery disease (CAD) or atherosclerotic heart disease is one of the most common types of cardiovascular disease. Although percutaneous coronary intervention?[PCI or percutaneous transluminal coronary angioplasty (PTCA)] is a mature, well-established technique used to treat atherosclerotic heart disease, its long?term therapeutic effects are compromised by a high incidence of vascular restenosis?(RS) following angioplasty. In our previous study, we found that the principal gap junction protein, connexin?43?(Cx43), in vascular smooth muscle cells (VSMCs) was involved in the development of vascular RS following angioplasty-induced balloon injury. However, the exact role action of Cx43 in vascular RS remains unclear. In the present study, we aimed to further examine whether the knockdown of Cx43 attenuates the development of vascular RS through the inhibition of the proliferation and migration of VSMCs. We found that the use of a lentiviral vector expressing shRNA targeting Cx43 (Cx43?RNAi-LV) efficiently silenced the mRNA and protein expression of Cx43 in cultured VSMCs. In addition, MTT and Transwell assays were used to examined the proliferation and migration of the VSMCs, respectively. The results revealed that the knockdown of Cx43 by Cx43-RNAi-LV at a multiplicity of infection?(MOI) of?100 significantly inhibited the proliferation and migration of the VSMCs in?vitro. Notably, the knockdown of Cx43 also effectively attenuated the development of vascular RS and intimal hyperplasia following balloon injury in?vivo. Taken together, our data suggest that Cx43 is involved in the development of vascular RS and intimal hyperplasia through the regulation of the proliferation and migration of VSMCs. Thus, the present study provides new insight into the pathogenesis of vascular RS, and suggests that further comfirms that Cx43 may well be a novel potential pharmacological target for preventing vascular RS following PCI.