• Bing-Hsiean Tzeng, Yen-Hui Chen, Ching-Hui Huang, Shin-Shiou Lin, Kuan-Rong Lee, and Chien-Chang Chen.
• Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan.
• Cardiovasc. Res. 2012 Dec 1; 96 (3): 533-42.

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(v)3.2(-/-) but not Ca(v)3.1(-/-) mice, indicating a critical role of Ca(v)3.1 in neointimal formation. In addition, we found a significant increase of Ca(v)3.1 mRNA and protein in injured arteries. Ca(v)3.1 knockout or knockdown (shCa(v)3.1) reduced VSMC proliferation. Since T-channels are expressed predominantly in the G(1) and S phases in VSMCs, we examined whether an abnormal G(1)/S transition was the cause of the reduced cell proliferation in shCa(v)3.1 VSMCs. We found a disrupted expression of cyclin E in shCa(v)3.1 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.ConclusionCa(v)3.1 is required for VSMC proliferation during neointimal formation, and blocking of Ca(v)3.1 may be beneficial for preventing restenosis.

61 keywords...

hide…