PMID- 28475806
OWN - NLM
STAT- MEDLINE
DCOM- 20171204
LR  - 20211204
IS  - 1569-9285 (Electronic)
IS  - 1569-9285 (Linking)
VI  - 25
IP  - 2
DP  - 2017 Aug 1
TI  - Rapamycin reduced pulmonary vascular remodelling by inhibiting cell proliferation 
      via Akt/mTOR signalling pathway down-regulation in the carotid artery-jugular 
      vein shunt pulmonary hypertension rat model.
PG  - 206-211
LID - 10.1093/icvts/ivx053 [doi]
AB  - OBJECTIVES: Pulmonary arterial hypertension (PAH) is a common complication of 
      congenital heart disease. However, effective treatments for PAH are rare. This 
      study aimed to investigate the inhibitory effects of rapamycin on PAH in the 
      carotid artery-jugular vein (CA-JV) shunt PAH rat model as well as the mechanism 
      underlying these effects. METHODS: Twenty-four Sprague-Dawley rats were 
      randomized into the following 3 groups: a control group, a CA-JV shunt group and 
      a treatment group. Rapamycin (2 mg/kg/day) was administered to the treatment 
      group, and placebo was administered to the CA-JV shunt group. Haemodynamic 
      evaluations, pulmonary tissue samplings for morphometry and immunofluorescence 
      and western blot analyses were performed to evaluate the effects of rapamycin on 
      PAH. RESULTS: Rapamycin attenuated the increase of right ventricular systolic 
      pressure (RVSP) and the right ventricular (RV) hypertrophy (RVSP: CA-JV vs 
      CA-JV + rapamycin, P = 0.017; RV: CA-JV vs CA-JV + rapamycin, P = 0.022), as well 
      as the intrapulmonary vessel thickening (thickness index: CA-JV vs 
      CA-JV + rapamycin, P = 0.028; area index: CA-JV vs CA-JV + rapamycin, P = 0.014), 
      induced by overcirculation of the pulmonary vasculature in the CA-JV 
      shunt-induced PAH rat model. Rapamycin decreased the expression level of the 
      indicated cell proliferation marker (alpha-smooth muscle actin) in the lung vessel 
      and mechanistic target of rapamycin (mTOR) pathway components (p-mTOR: CA-JV vs 
      CA-JV + rapamycin, P = 0.004; p-Raptor: CA-JV vs CA-JV + rapamycin, P = 0.000; 
      p-S6K1: CA-JV vs CA-JV + rapamycin, P = 0.000; p-Akt: CA-JV vs CA-JV + rapamycin, 
      P = 0.001; p-Rheb: CA-JV vs CA-JV + rapamycin, P = 0.000) in pulmonary tissue. 
      CONCLUSIONS: Rapamycin reduced pulmonary vascular remodelling by inhibiting cell 
      proliferation via Akt/mTOR signalling pathway down-regulation in the CA-JV 
      shunt-induced PAH model in rats. Thus, rapamycin may be a novel candidate drug 
      for the treatment of PAH.
CI  - (c) The Author 2017. Published by Oxford University Press on behalf of the European 
      Association for Cardio-Thoracic Surgery. All rights reserved.
FAU - Ma, Xiaofan
AU  - Ma X
AD  - Department of Paediatric and Congenital Cardiac Surgery, The First Affiliated 
      Hospital of Sun Yat-sen University, Guangzhou, China.
FAU - Yao, Jianping
AU  - Yao J
AD  - Department of Paediatric and Congenital Cardiac Surgery, The First Affiliated 
      Hospital of Sun Yat-sen University, Guangzhou, China.
FAU - Yue, Yuan
AU  - Yue Y
AD  - Department of Paediatric and Congenital Cardiac Surgery, The First Affiliated 
      Hospital of Sun Yat-sen University, Guangzhou, China.
FAU - Du, Shangming
AU  - Du S
AD  - Department of Paediatric and Congenital Cardiac Surgery, The First Affiliated 
      Hospital of Sun Yat-sen University, Guangzhou, China.
FAU - Qin, Han
AU  - Qin H
AD  - Department of Paediatric and Congenital Cardiac Surgery, The First Affiliated 
      Hospital of Sun Yat-sen University, Guangzhou, China.
FAU - Hou, Jian
AU  - Hou J
AD  - Department of Paediatric and Congenital Cardiac Surgery, The First Affiliated 
      Hospital of Sun Yat-sen University, Guangzhou, China.
FAU - Wu, Zhongkai
AU  - Wu Z
AD  - Department of Paediatric and Congenital Cardiac Surgery, The First Affiliated 
      Hospital of Sun Yat-sen University, Guangzhou, China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Interact Cardiovasc Thorac Surg
JT  - Interactive cardiovascular and thoracic surgery
JID - 101158399
RN  - 0 (Immunosuppressive Agents)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Arteriovenous Shunt, Surgical/methods
MH  - Blotting, Western
MH  - Carotid Artery, Common/surgery
MH  - Cell Proliferation/drug effects
MH  - Disease Models, Animal
MH  - *Down-Regulation
MH  - Hypertension, Pulmonary/metabolism/*physiopathology/surgery
MH  - Immunosuppressive Agents/pharmacology
MH  - Jugular Veins/surgery
MH  - Male
MH  - Pulmonary Artery/metabolism/pathology/*physiopathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases/*biosynthesis
MH  - Vascular Remodeling/*drug effects
OTO - NOTNLM
OT  - Cell proliferation
OT  - Pulmonary arterial hypertension
OT  - Rapamycin
OT  - mTOR pathway
EDAT- 2017/05/06 06:00
MHDA- 2017/12/05 06:00
CRDT- 2017/05/06 06:00
PHST- 2016/08/24 00:00 [received]
PHST- 2017/01/24 00:00 [accepted]
PHST- 2017/05/06 06:00 [pubmed]
PHST- 2017/12/05 06:00 [medline]
PHST- 2017/05/06 06:00 [entrez]
AID - 3798547 [pii]
AID - 10.1093/icvts/ivx053 [doi]
PST - ppublish
SO  - Interact Cardiovasc Thorac Surg. 2017 Aug 1;25(2):206-211. doi: 
      10.1093/icvts/ivx053.