The Cav3.1 T-type calcium channel is required for neointimal formation in response to vascular injury in mice

摘要

AimsRestenosis is an undesirable consequence following percutaneous vascular interventions. However, the current strategy for preventing restenosis is inadequate. The aim of this study was to investigate the role of low-voltage gated T-type calcium channels in regulating vascular smooth muscle cell (VSMC) proliferation during neointimal formation.Methods and resultsWire injury of mice carotid arteries resulted in neointimal formation in the wild-type and Ca v3.2-/- but not Cav3.1-/- mice, indicating a critical role of Cav3.1 in neointimal formation. In addition, we found a significant increase of Cav3.1 mRNA and protein in injured arteries. Cav3.1 knockout or knockdown (shCa v3.1) reduced VSMC proliferation. Since T-channels are expressed predominantly in the G1 and S phases in VSMCs, we examined whether an abnormal G1/S transition was the cause of the reduced cell proliferation in shCav3.1 VSMCs. We found a disrupted expression of cyclin E in shCav3.1 VSMCs, and calmodulin agonist CALP1 partially rescued the defective cell proliferation. Furthermore, we demonstrated that infusion of NNC55-0396, a selective T-channel blocker, inhibited neointimal formation in wild-type mice.ConclusionCav3.1 is required for VSMC proliferation during neointimal formation, and blocking of Cav3.1 may be beneficial for preventing restenosis.