title: SIRT1 and FOXO Mediate Contractile Differentiation of Vascular Smooth Muscle Cells under Cyclic Stretch.
abstract: OBJECTIVE
  Physiological mechanical stretch in vivo helps to maintain the quiescent contractile differentiation of vascular smooth muscle cells (VSMCs), but the underlying mechanisms are still unclear. Here, we investigated the effects of SIRT1 in VSMC differentiation in response to mechanical cyclic stretch.
  
  
  RESULTS
  Rat VSMCs were subjected to 10%-1.25Hz-cyclic stretch in vitro using a FX-4000T system. The data indicated that the expression of contractile markers, including α-actin, calponin and SM22α, was significantly enhanced in VSMCs that were subjected to cyclic stretch compared to the static controls. The expression of SIRT1 and FOXO3a was increased by the stretch, but the expression of FOXO4 was decreased. Decreasing SIRT1 by siRNA transfection attenuated the stretch-induced expression of contractile VSMC markers and FOXO3a. Furthermore, increasing SIRT1 by either treatment with activator resveratrol or transfection with a plasmid to induce overexpression increased the expression of FOXO3a and contractile markers, and decreased the expression of FOXO4 in VSMCs. Similar trends were observed in VSMCs of SIRT1 (+/-) knockout mice. The overexpression of FOXO3a promoted the expression of contractile markers in VSMCs, while the overexpression of FOXO4 demonstrated the opposite effect.
  
  
  CONCLUSIONS
  Our results indicated that physiological cyclic stretch promotes the contractile differentiation of VSMCs via the SIRT1/FOXO pathways and thus contributes to maintaining vascular homeostasis.
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Yan
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Si-Guo
authors.initials: SG
authors.lastname: Chen
authors.forename: Li-Zhi
authors.initials: LZ
authors.lastname: Gao
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Bao-Rong
authors.initials: BR
authors.lastname: Shen
authors.forename: Hai-Chao
authors.initials: HC
authors.lastname: Han
authors.forename: Ying-Xin
authors.initials: YX
authors.lastname: Qi
authors.forename: Zong-Lai
authors.initials: ZL
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism; D009119:Muscle Contraction; D009124:Muscle Proteins / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology; D013314:Stress, Mechanical; D015854:Up-Regulation / Q000187:drug effects; D000096985:Calponins
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D008840:Microfilament Proteins; D009124:Muscle Proteins; D034741:RNA, Small Interfering; D000077185:Resveratrol; D056564:Sirtuin 1; D013267:Stilbenes; D000096985:Calponins; C474033:FoxO3 protein, mouse; C525394:FoxO4 protein, mouse; C051615:transgelin; C470545:Sirt1 protein, mouse