title: The Ca(v)3.1 T-type calcium channel is required for neointimal formation in response to vascular injury in mice.
abstract: OBJECTIVE
  Restenosis 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.
  
  
  RESULTS
  Wire 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.
  
  
  CONCLUSIONS
  Ca(v)3.1 is required for VSMC proliferation during neointimal formation, and blocking of Ca(v)3.1 may be beneficial for preventing restenosis.
authors.affiliation: Graduate Institute of Life Sciences,  National Defense Medical Center, Taipei 11490,  Taiwan.
authors.forename: Bing-Hsiean
authors.initials: BH
authors.lastname: Tzeng
authors.forename: Yen-Hui
authors.initials: YH
authors.lastname: Chen
authors.forename: Ching-Hui
authors.initials: CH
authors.lastname: Huang
authors.forename: Shin-Shiou
authors.initials: SS
authors.lastname: Lin
authors.forename: Kuan-Rong
authors.initials: KR
authors.lastname: Lee
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Chen
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002147:Calmodulin / Q000819:agonists / Q000378:metabolism; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology; D020212:Carotid Artery Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation; D002478:Cells, Cultured; D019927:Cyclin E / Q000378:metabolism; D003521:Cyclopropanes / Q000494:pharmacology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009281:Naphthalenes / Q000494:pharmacology; D058426:Neointima; D009842:Oligopeptides / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D057772:Vascular System Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D001562:Benzimidazoles; C498197:Cacna1g protein, mouse; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D002147:Calmodulin; D019927:Cyclin E; D003521:Cyclopropanes; D009281:Naphthalenes; D009842:Oligopeptides; D012333:RNA, Messenger; C412708:calcium-like peptide CALP1; C484287:NNC 55-0396