PMID- 19109527
OWN - NLM
STAT- MEDLINE
DCOM- 20090427
LR  - 20211020
IS  - 0363-6143 (Print)
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 296
IP  - 3
DP  - 2009 Mar
TI  - Simvastatin enhances bone marrow stromal cell differentiation into endothelial 
      cells via notch signaling pathway.
PG  - C535-43
LID - 10.1152/ajpcell.00310.2008 [doi]
AB  - Bone marrow stromal cells (BMSCs) are capable of differentiating into multiple 
      cell lineages including endothelial cells. Simvastatin, an HMG-CoA reductase 
      inhibitor that is used as a cholesterol-lowering agent, promotes endothelial 
      differentiation from epithelial progenitor cells (EPC). The Notch signaling 
      pathway, which plays a key role in multiple cell functions such as 
      differentiation, proliferation, and apoptosis, can be regulated by simvastatin. 
      Therefore, we examined the effect of simvastatin on BMSC differentiation into 
      endothelial cells and the underlying mechanisms involved in this process. We 
      observed that simvastatin stimulation of rat BMSCs resulted in significantly 
      increased expression of endothelial-specific genes and proteins, including von 
      Willebrand factor (vWF), CD31, vascular endothelial-cadherin (VE-cadherin), 
      vascular endothelial growth factor receptor-2 (VEGFR2, Flk-1), and VEGF receptor 
      1 (VEGFR-1, Flt-1). Simvastatin also significantly increased capillary tubelike 
      formation of the BMSCs. In addition, the intracellular cleavage of Notch (NICD) 
      was markedly enhanced by simvastatin in BMSCs. Incubation of BMSCs with a 
      gamma-secretase inhibitor, or Notch1 small interfering RNA (siRNA) that 
      significantly inhibited the formation of NICD, blocked the expression of 
      endothelial-specific markers in BMSCs and their differentiation into functional 
      endothelial cells. These data suggest that simvastatin induces rat BMSCs 
      differentiation into endothelial cells via a Notch signaling pathway.
FAU - Xu, Jian
AU  - Xu J
AD  - Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, 
      Nanjing, China.
FAU - Liu, Xinfeng
AU  - Liu X
FAU - Chen, Jieli
AU  - Chen J
FAU - Zacharek, Alex
AU  - Zacharek A
FAU - Cui, Xu
AU  - Cui X
FAU - Savant-Bhonsale, Smita
AU  - Savant-Bhonsale S
FAU - Liu, Zhenguo
AU  - Liu Z
FAU - Chopp, Michael
AU  - Chopp M
LA  - eng
GR  - R01 NS047682-04/NS/NINDS NIH HHS/United States
GR  - R01 AG-031811/AG/NIA NIH HHS/United States
GR  - R01 NS-047682/NS/NINDS NIH HHS/United States
GR  - R01 NS047682/NS/NINDS NIH HHS/United States
GR  - P01 NS-23393/NS/NINDS NIH HHS/United States
GR  - K08HL-0755410/HL/NHLBI NIH HHS/United States
GR  - NS-42345/NS/NINDS NIH HHS/United States
GR  - NS-23393/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20081224
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Biomarkers)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Notch)
RN  - AGG2FN16EV (Simvastatin)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
SB  - IM
MH  - Amyloid Precursor Protein Secretases/antagonists & inhibitors/metabolism
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Bone Marrow Cells/*drug effects/metabolism
MH  - Cell Differentiation/*drug effects
MH  - Cells, Cultured
MH  - Endothelial Cells/*drug effects/metabolism
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - Neovascularization, Physiologic/drug effects
MH  - Protein Processing, Post-Translational/drug effects
MH  - RNA Interference
MH  - RNA, Small Interfering
MH  - Rats
MH  - Receptors, Notch/genetics/*metabolism
MH  - Signal Transduction/*drug effects
MH  - Simvastatin/*pharmacology
MH  - Stem Cells/*drug effects/metabolism
MH  - Stromal Cells/*drug effects/metabolism
MH  - Time Factors
PMC - PMC2660258
EDAT- 2008/12/26 09:00
MHDA- 2009/04/28 09:00
PMCR- 2010/03/01
CRDT- 2008/12/26 09:00
PHST- 2008/12/26 09:00 [entrez]
PHST- 2008/12/26 09:00 [pubmed]
PHST- 2009/04/28 09:00 [medline]
PHST- 2010/03/01 00:00 [pmc-release]
AID - 00310.2008 [pii]
AID - C-00310-2008 [pii]
AID - 10.1152/ajpcell.00310.2008 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2009 Mar;296(3):C535-43. doi: 
      10.1152/ajpcell.00310.2008. Epub 2008 Dec 24.