PMID- 24518659
OWN - NLM
STAT- MEDLINE
DCOM- 20140624
LR  - 20220331
IS  - 1916-7075 (Electronic)
IS  - 0828-282X (Linking)
VI  - 30
IP  - 5
DP  - 2014 May
TI  - The mammalian target of rapamycin signalling pathway is involved in osteoblastic 
      differentiation of vascular smooth muscle cells.
PG  - 568-75
LID - S0828-282X(13)01636-X [pii]
LID - 10.1016/j.cjca.2013.11.005 [doi]
AB  - BACKGROUND: Vascular calcification is a major risk factor for cardiovascular 
      diseases. Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) is 
      a key step in vascular calcification, but the molecular mechanisms driving the 
      differentiation remain elusive. In this study, the involvement of mammalian 
      target of rapamycin (mTOR) signalling in osteoblastic differentiation of VSMCs is 
      investigated. METHODS: Calcification of VSMCs was induced in vitro using 
      beta-glycerophosphate (beta-GP). Real-time polymerase chain reaction was used to 
      measure messenger RNA (mRNA) expression, and Western blot was used to detect 
      protein expression. Inhibition of mTOR expression was established by small 
      interfering RNA (siRNA) and mTOR inhibitors. RESULTS: The model for osteoblastic 
      differentiation of VSMCs was established in vitro by treating mouse VSMCs with 10 
      mM beta-GP for 3-15 days. Overexpression of mTOR was observed in differentiated 
      VSMCs. Downregulation of mTOR by siRNA or rapamycin significantly inhibited 
      osteoblastic differentiation of VSMCs and decreased the expression and 
      phosphorylation of mTOR and P70 ribosomal S6 kinase in a time- and 
      concentration-dependent manner. Furthermore, adiponectin inhibited the mRNA and 
      protein expression of mTOR in beta-GP-treated VSMCs in a time- and 
      concentration-dependent manner. CONCLUSIONS: mTOR signalling plays a crucial role 
      in the osteoblastic differentiation of VSMCs. Rapamycin and adiponectin might 
      inhibit vascular calcification through regulation of the mTOR pathway.
CI  - Copyright (c) 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All 
      rights reserved.
FAU - Zhan, Jun-Kun
AU  - Zhan JK
AD  - Department of Geriatrics, Second Xiangya Hospital, Institute of Aging and 
      Geriatrics, Central South University, Changsha, Hunan, P.R. China.
FAU - Wang, Yan-Jiao
AU  - Wang YJ
AD  - Department of Geriatrics, Second Xiangya Hospital, Institute of Aging and 
      Geriatrics, Central South University, Changsha, Hunan, P.R. China.
FAU - Wang, Yi
AU  - Wang Y
AD  - Department of Geriatrics, Second Xiangya Hospital, Institute of Aging and 
      Geriatrics, Central South University, Changsha, Hunan, P.R. China.
FAU - Wang, Sha
AU  - Wang S
AD  - Department of Geriatrics, Second Xiangya Hospital, Institute of Aging and 
      Geriatrics, Central South University, Changsha, Hunan, P.R. China.
FAU - Tan, Pan
AU  - Tan P
AD  - Department of Geriatrics, Second Xiangya Hospital, Institute of Aging and 
      Geriatrics, Central South University, Changsha, Hunan, P.R. China.
FAU - Huang, Wu
AU  - Huang W
AD  - Department of Geriatrics, Second Xiangya Hospital, Institute of Aging and 
      Geriatrics, Central South University, Changsha, Hunan, P.R. China.
FAU - Liu, You-Shuo
AU  - Liu YS
AD  - Department of Geriatrics, Second Xiangya Hospital, Institute of Aging and 
      Geriatrics, Central South University, Changsha, Hunan, P.R. China. Electronic 
      address: Liuyoushuo@yeah.net.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131108
PL  - England
TA  - Can J Cardiol
JT  - The Canadian journal of cardiology
JID - 8510280
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
CIN - Can J Cardiol. 2014 May;30(5):482-4. PMID: 24698657
MH  - Animals
MH  - Blotting, Western
MH  - Cell Differentiation/drug effects
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/*drug effects
MH  - Humans
MH  - Immunosuppressive Agents/pharmacology
MH  - Mice
MH  - Muscle, Smooth, Vascular/drug effects/*pathology
MH  - Osteoblasts/metabolism/*pathology
MH  - RNA, Messenger/*genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Signal Transduction/drug effects
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases/biosynthesis/*genetics
MH  - Vascular Calcification/*drug therapy/genetics/pathology
EDAT- 2014/02/13 06:00
MHDA- 2014/06/25 06:00
CRDT- 2014/02/13 06:00
PHST- 2013/09/10 00:00 [received]
PHST- 2013/10/20 00:00 [revised]
PHST- 2013/11/04 00:00 [accepted]
PHST- 2014/02/13 06:00 [entrez]
PHST- 2014/02/13 06:00 [pubmed]
PHST- 2014/06/25 06:00 [medline]
AID - S0828-282X(13)01636-X [pii]
AID - 10.1016/j.cjca.2013.11.005 [doi]
PST - ppublish
SO  - Can J Cardiol. 2014 May;30(5):568-75. doi: 10.1016/j.cjca.2013.11.005. Epub 2013 
      Nov 8.