PMID- 37873631
OWN - NLM
STAT- MEDLINE
DCOM- 20231030
LR  - 20231030
IS  - 1598-6357 (Electronic)
IS  - 1011-8934 (Print)
IS  - 1011-8934 (Linking)
VI  - 38
IP  - 41
DP  - 2023 Oct 23
TI  - Far-Infrared Irradiation Decreases Proliferation in Basal and PDGF-Stimulated 
      VSMCs Through AMPK-Mediated Inhibition of mTOR/p70S6K Signaling Axis.
PG  - e335
LID - 10.3346/jkms.2023.38.e335 [doi]
LID - e335
AB  - BACKGROUND: Far-infrared (FIR) irradiation has been reported to improve diverse 
      cardiovascular diseases, including heart failure, hypertension, and 
      atherosclerosis. The dysregulated proliferation of vascular smooth muscle cells 
      (VSMCs) is well established to contribute to developing occlusive vascular 
      diseases such as atherosclerosis and in-stent restenosis. However, the effects of 
      FIR irradiation on VSMC proliferation and the underlying mechanism are unclear. 
      This study investigated the molecular mechanism through which FIR irradiation 
      inhibited VSMC proliferation. METHODS: We performed cell proliferation and cell 
      death assay, adenosine 5'-triphosphate (ATP) assay, inhibitor studies, 
      transfection of dominant negative (dn)-AMP-activated protein kinase (AMPK) alpha1 
      gene, and western blot analyses. We also conducted confocal microscopic image 
      analyses and ex vivo studies using isolated rat aortas. RESULTS: FIR irradiation 
      for 30 minutes decreased VSMC proliferation without altering the cell death. 
      Furthermore, FIR irradiation accompanied decreases in phosphorylation of the 
      mammalian target of rapamycin (mTOR) at Ser2448 (p-mTOR-Ser(2448)) and p70 S6 
      kinase (p70S6K) at Thr389 (p-p70S6K-Thr(389)). The phosphorylation of AMPK at 
      Thr172 (p-AMPK-Thr(172)) was increased in FIR-irradiated VSMCs, which was 
      accompanied by a decreased cellular ATP level. Similar to in vitro results, FIR 
      irradiation increased p-AMPK-Thr(172) and decreased p-mTOR-Ser(2448) and 
      p-p70S6K-Thr(389) in isolated rat aortas. Pre-treatment with compound C, a 
      specific AMPK inhibitor, or ectopic expression of dn-AMPKalpha1 gene, significantly 
      reversed FIR irradiation-decreased VSMC proliferation, p-mTOR-Ser(2448), and 
      p-p70S6K-Thr(389). On the other hand, hyperthermal stimulus (39 degrees C) did not alter 
      VSMC proliferation, cellular ATP level, and AMPK/mTOR/p70S6K phosphorylation. 
      Finally, FIR irradiation attenuated platelet-derived growth factor 
      (PDGF)-stimulated VSMC proliferation by increasing p-AMPK-Thr(172), and 
      decreasing p-mTOR-Ser(2448) and p-p70S6K-Thr(389) in PDGF-induced in vitro 
      atherosclerosis model. CONCLUSION: These results show that FIR irradiation 
      decreases the basal and PDGF-stimulated VSMC proliferation, at least in part, by 
      the AMPK-mediated inhibition of mTOR/p70S6K signaling axis irrespective of its 
      hyperthermal effect. These observations suggest that FIR therapy can be used to 
      treat arterial narrowing diseases, including atherosclerosis and in-stent 
      restenosis.
CI  - (c) 2023 The Korean Academy of Medical Sciences.
FAU - Hwang, Yun-Jin
AU  - Hwang YJ
AUID- ORCID: 0000-0002-7577-0865
AD  - Department of Pharmacology, College of Medicine, Yeungnam University, Daegu, 
      Korea.
FAU - Park, Jung-Hyun
AU  - Park JH
AUID- ORCID: 0000-0001-9060-6935
AD  - AbT R&D Center, AZothBio Inc., Hanam, Korea.
FAU - Cho, Du-Hyong
AU  - Cho DH
AUID- ORCID: 0000-0002-9891-1464
AD  - Department of Pharmacology, College of Medicine, Yeungnam University, Daegu, 
      Korea. biohyong@hanmail.net.
LA  - eng
GR  - 2022R1F1A1069879/NRF/National Research Foundation of Korea/Korea
PT  - Journal Article
DEP - 20231023
PL  - Korea (South)
TA  - J Korean Med Sci
JT  - Journal of Korean medical science
JID - 8703518
RN  - 0 (Platelet-Derived Growth Factor)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - W36ZG6FT64 (Sirolimus)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.1.1 (mTOR protein, rat)
SB  - IM
MH  - Rats
MH  - Animals
MH  - Platelet-Derived Growth Factor/pharmacology
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Muscle, Smooth, Vascular
MH  - Sirolimus/pharmacology
MH  - *Coronary Restenosis
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Cell Proliferation
MH  - Phosphorylation
MH  - Adenosine Triphosphate/metabolism/pharmacology
MH  - *Atherosclerosis
MH  - Mammals/metabolism
PMC - PMC10593596
OTO - NOTNLM
OT  - AMP-Activated Protein Kinase
OT  - Far-Infrared Irradiation
OT  - Mammalian Target of Rapamycin
OT  - Proliferation
OT  - Vascular Smooth Muscle Cells
OT  - p70 S6 Kinase
COIS- The authors have no potential conflicts of interest to disclose.
EDAT- 2023/10/24 06:41
MHDA- 2023/10/30 06:47
PMCR- 2023/10/23
CRDT- 2023/10/24 04:42
PHST- 2023/04/05 00:00 [received]
PHST- 2023/06/15 00:00 [accepted]
PHST- 2023/10/30 06:47 [medline]
PHST- 2023/10/24 06:41 [pubmed]
PHST- 2023/10/24 04:42 [entrez]
PHST- 2023/10/23 00:00 [pmc-release]
AID - 38.e335 [pii]
AID - 10.3346/jkms.2023.38.e335 [doi]
PST - epublish
SO  - J Korean Med Sci. 2023 Oct 23;38(41):e335. doi: 10.3346/jkms.2023.38.e335.