title: The protective effect of GLP-1 analogue in arterial calcification through attenuating osteoblastic differentiation of human VSMCs.
abstract: BACKGROUND
  Arterial calcification is a common event in cardiovascular pathogenesis. Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) is the most important cytopathologic foundation of arterial calcification. Glucagon-like peptide-1 (GLP-1) exerts multiple cardioprotective actions beyond insulinotropic effects through GLP-1 receptor (GLP-1R). However, whether GLP-1 regulates osteoblastic differentiation of VSMCs and associated molecular mechanisms has not been clarified.
  
  
  METHODS
  The human VSMC differentiation model was established by beta-glycerophosphate (β-GP) induction. The mineralization was measured by Alizarin Red S staining. Protein expression and phosphorylation were detected by Western blot or immunofluorescence. GLP-1R gene expression was silenced by siRNA.
  
  
  RESULTS
  The GLP-1 analogue liraglutide dose- and time-dependently inhibited the protein expression of osteoblastic differentiation markers alkaline phosphatase (ALP), osteocalcin (OC), and Runt-related transcription factor 2 (Runx2), phosphorylation of PI3K, Akt, mTOR, and S6K1. Silencing of GLP-1R gene expression by siRNA significantly blocked the effects of liraglutide in ALP protein expression and PI3K/Akt phosphorylation.
  
  
  CONCLUSIONS
  GLP-1 analogue liraglutide attenuates the osteoblastic differentiation and calcification of human VSMCs through its receptor and subsequent activation of PI3K/Akt/mTOR/S6K1 signaling. GLP-1 analogues may be potential agents for the treatment of cardiovascular diseases.
authors.affiliation: Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
authors.forename: Jun-Kun
authors.initials: JK
authors.lastname: Zhan
authors.affiliation: Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
authors.forename: Yan-Jiao
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Tang
authors.affiliation: Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
authors.forename: Pan
authors.initials: P
authors.lastname: Tan
authors.affiliation: Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China.
authors.forename: Wu
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China. Electronic address: Liuyoushuo@yeah.net.
authors.forename: You-Shuo
authors.initials: YS
authors.lastname: Liu
mesh_terms: D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D006801:Humans; D000069450:Liraglutide / Q000494:pharmacology; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D061205:Vascular Calcification / Q000378:metabolism / Q000517:prevention & control*
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1
keywords: Akt; Calcification; Glucagon-like peptide-1; Osteoblastic differentiation; PI3K; Vascular smooth muscle cells; mTOR; siRNA