title: Effect of sarcosine on endothelial function relevant to angiogenesis.
abstract: OBJECTIVE
  Endothelial cells (ECs) respond to changes in metabolic status and switch over to angiogenic phenotype. There are several metabolites known to mediate this transition; however, the effect of sarcosine that accumulates in invasive prostate cancer is not known. The objective of the study was to examine whether sarcosine influences EC function and affects angiogenesis.
  
  
  METHODS
  The effect of sarcosine was studied using different model systems including chick chorioallantoic membrane (CAM), rat aortic rings in culture, and human umbilical vein ECs (HUVECs) in culture. The statistical significance of difference was analyzed by one-way analysis of variance (ANOVA) and Student's t-test using GraphPad 5 software.
  
  
  RESULTS
  Increased vascularization in CAM, increased endothelial sprouting in rat aortic rings in culture, and increased expression of CD31 and E-selectin suggested a possible angiogenic effect of sarcosine. Sarcosine modulated expression of angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). In ECs in culture LY294002, an inhibitor of phosphatidylinositol-3-kinase (PI3K)/Akt pathway and rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) reversed the effect of sarcosine. Further, sarcosine induced upregulation and activation of Akt in HUVECs.
  
  
  CONCLUSIONS
  These results suggest that sarcosine modulates EC function relevant to angiogenesis through modulation of PI3K/Akt/mTOR pathway.
authors.affiliation: Department of Computational Biology and Bioinformatics; Department of Biochemistry, University of Kerala, Thiruvananthapuram, Kerala, India.
authors.forename: Peruman R
authors.initials: PR
authors.lastname: Sudhakaran
authors.forename: Sheela
authors.initials: S
authors.lastname: Binu
authors.forename: Sasikumar J
authors.initials: SJ
authors.lastname: Soumya
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D002642:Chick Embryo; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D012521:Sarcosine / Q000494:pharmacology*
chemical_list: D043925:Angiogenesis Inducing Agents; D012521:Sarcosine