PMID- 31336911
OWN - NLM
STAT- MEDLINE
DCOM- 20191227
LR  - 20200225
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 20
IP  - 14
DP  - 2019 Jul 12
TI  - Glucagon-Like Peptide-1 Receptor Agonist Attenuates Autophagy to Ameliorate 
      Pulmonary Arterial Hypertension through Drp1/NOX- and Atg-5/Atg-7/Beclin-1/LC3beta 
      Pathways.
LID - 10.3390/ijms20143435 [doi]
LID - 3435
AB  - Mitochondrial dysfunction is associated with cardiovascular diseases and 
      diabetes. Pulmonary arterial hypertension (PAH) is characterized by pulmonary 
      vascular remodeling, and the abnormal proliferation, apoptosis and migration of 
      pulmonary arterial smooth muscle cells (PASMCs). The glucagon-like peptide-1 
      (GLP-1) receptor agonist, liraglutide, has been shown to prevent pulmonary 
      hypertension in monocrotaline-exposed rats. The aim of this study was to 
      investigate the effect of liraglutide on autophagy, mitochondrial stress and 
      apoptosis induced by platelet-derived growth factor BB (PDGF-BB). PASMCs were 
      exposed to PDGF-BB, and changes in mitochondrial morphology, fusion-associated 
      protein markers, and reactive oxygen species (ROS) production were examined. 
      Autophagy was assessed according to the expressions of microtubule-associated 
      protein light chain 3 (LC3)-II, LC3 puncta and Beclin-1. Western blot analysis 
      was used to assess apoptosis, mitochondrial stress and autophagy markers. 
      Liraglutide significantly inhibited PDGF-BB proliferation, migration and motility 
      in PASMCs. PDGF-BB-induced ROS production was mitigated by liraglutide. 
      Liraglutide increased the expression of alpha-smooth muscle actin (alpha-SMA) and 
      decreased the expression of p-Yes-associated protein (p-YAP), inhibited 
      autophagy-related protein (Atg)-5, Atg-7, Beclin-1 and the formation of LC3-beta and 
      mitochondrial fusion protein dynamin-related (Drp)1. Therefore, liraglutide can 
      mitigate the proliferation of PASMCs via inhibiting cellular Drp1/nicotinamide 
      adenine dinucleotide phosphate (NADPH) oxidases (NOX) pathways and 
      Atg-5/Atg-7/Beclin-1/LC3beta-dependent pathways of autophagy in PAH.
FAU - Wu, Yi-Chia
AU  - Wu YC
AD  - Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University 
      Hospital, Kaohsiung 80708, Taiwan.
AD  - Ph.D. Program in Translational Medicine, Kaohsiung Medical University and 
      Academia Sinica, Taipei 11564, Taiwan.
AD  - Research Center of Regenerative Medicine and Cell Therapy, Kaohsiung Medical 
      University, Kaohsiung 80708, Taiwan.
AD  - Translational Research Center, Department of Medical Research, Kaohsiung Medical 
      University Hospital, Kaohsiung 80708, Taiwan.
FAU - Wang, Wei-Ting
AU  - Wang WT
AD  - Center of Teaching and Research, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 
      80145, Taiwan.
FAU - Lee, Su-Shin
AU  - Lee SS
AD  - Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University 
      Hospital, Kaohsiung 80708, Taiwan.
AD  - Research Center of Regenerative Medicine and Cell Therapy, Kaohsiung Medical 
      University, Kaohsiung 80708, Taiwan.
AD  - Department of Surgery, School of Medicine, College of Medicine, Kaohsiung Medical 
      University, Kaohsiung 80708, Taiwan.
FAU - Kuo, Yur-Ren
AU  - Kuo YR
AD  - Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University 
      Hospital, Kaohsiung 80708, Taiwan.
AD  - Research Center of Regenerative Medicine and Cell Therapy, Kaohsiung Medical 
      University, Kaohsiung 80708, Taiwan.
AD  - Department of Surgery, School of Medicine, College of Medicine, Kaohsiung Medical 
      University, Kaohsiung 80708, Taiwan.
FAU - Wang, Ya-Chin
AU  - Wang YC
AD  - Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University 
      Hospital, Kaohsiung 80708, Taiwan.
FAU - Yen, Shih-Jung
AU  - Yen SJ
AD  - Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 
      80145, Taiwan.
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Kaohsiung Medical University Hospital, 807 Kaohsiung 80708, Taiwan.
FAU - Lee, Mei-Yueh
AU  - Lee MY
AUID- ORCID: 0000-0001-8950-064X
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Kaohsiung Medical University Hospital, 807 Kaohsiung 80708, Taiwan. 
      lovellelee@hotmail.com.
AD  - Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung 
      Medical University, Kaohsiung 80708, Taiwan. lovellelee@hotmail.com.
FAU - Yeh, Jwu-Lai
AU  - Yeh JL
AUID- ORCID: 0000-0001-7101-5865
AD  - Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung 
      Medical University, Kaohsiung 80708, Taiwan. jwulai@kmu.edu.tw.
AD  - Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 
      80708, Taiwan. jwulai@kmu.edu.tw.
LA  - eng
GR  - MOST 106-2314-B-650-009 and MOST 106-2320-B-037-010-MY3/Ministry of Science and 
      Technology/
GR  - KMTTH-104-033 and KMTTH -106-041/Kaohsiung Municipal Ta-Tung Hospital/
GR  - AS-TM-108-02-01/Translational Medical Research Program of Academia Sinica, 
      Taiwan/
PT  - Journal Article
DEP - 20190712
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Reactive Oxygen Species)
RN  - 1B56C968OA (Becaplermin)
RN  - 839I73S42A (Liraglutide)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Autophagy/*drug effects
MH  - Becaplermin/metabolism
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Glucagon-Like Peptide-1 Receptor/*agonists
MH  - Liraglutide/pharmacology
MH  - Male
MH  - Mitochondria/drug effects/metabolism
MH  - Mitochondrial Dynamics/drug effects
MH  - Models, Biological
MH  - Muscle, Smooth, Vascular/cytology/metabolism
MH  - Myocytes, Smooth Muscle/drug effects/metabolism
MH  - Pulmonary Arterial Hypertension/drug therapy/*etiology/*metabolism
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/*drug effects
PMC - PMC6678531
OTO - NOTNLM
OT  - GLP-1 receptor agonists
OT  - autophagy
OT  - liraglutide
OT  - mitochondria
OT  - pulmonary artery hypertension
COIS- The authors declare no conflict of interest.
EDAT- 2019/07/25 06:00
MHDA- 2019/12/28 06:00
PMCR- 2019/07/01
CRDT- 2019/07/25 06:00
PHST- 2019/06/27 00:00 [received]
PHST- 2019/07/09 00:00 [revised]
PHST- 2019/07/11 00:00 [accepted]
PHST- 2019/07/25 06:00 [entrez]
PHST- 2019/07/25 06:00 [pubmed]
PHST- 2019/12/28 06:00 [medline]
PHST- 2019/07/01 00:00 [pmc-release]
AID - ijms20143435 [pii]
AID - ijms-20-03435 [pii]
AID - 10.3390/ijms20143435 [doi]
PST - epublish
SO  - Int J Mol Sci. 2019 Jul 12;20(14):3435. doi: 10.3390/ijms20143435.