PMID- 35836818
OWN - NLM
STAT- MEDLINE
DCOM- 20220718
LR  - 20230111
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 12
IP  - 11
DP  - 2022
TI  - Arterial cyclic stretch regulates Lamtor1 and promotes neointimal hyperplasia via 
      circSlc8a1/miR-20a-5p axis in vein grafts.
PG  - 4851-4865
LID - 10.7150/thno.69551 [doi]
AB  - Rationale: Neointimal hyperplasia caused by dedifferentiation and proliferation 
      of venous smooth muscle cells (SMCs) is the major challenge for restenosis after 
      coronary artery bypass graft. Herein, we investigated the role of Lamtor1 in 
      neointimal formation and the regulatory mechanism of non-coding RNA underlying 
      this process. Methods: Using a "cuff" model, veins were grafted into arterial 
      system and Lamtor1 expression which was correlated with the activation of mTORC1 
      signaling and dedifferentiation of SMCs, were measured by Western blot. Whole 
      transcriptome deep sequencing (RNA-seq) of the grafted veins combined with 
      bioinformatic analysis identified highly conserved circSlc8a1 and its interaction 
      with miR-20a-5p, which may target Lamtor1. CircSlc8a1 was biochemically 
      characterized by Sanger sequencing and resistant to RNase R digestion. The 
      cytoplasmic location of circSlc8a1 was shown by fluorescence in situ 
      hybridization (FISH). RNA pull-down, luciferase assays and RNA 
      immunoprecipitation (RIP) with Ago2 assays were used to identify the interaction 
      circSlc8a1 with miR-20a-5p. Furthermore, arterial mechanical stretch (10% 
      elongation) was applied in vitro. Results:In vivo, Lamtor1 was significantly 
      enhanced in grafted vein and activated mTORC1 signaling to promote 
      dedifferentiation of SMCs. Arterial mechanical stretch (10% elongation) induced 
      circSlc8a1 expression and positively regulated Lamtor1, activated mTORC1 and 
      promoted SMC dedifferentiation and proliferation. Local injection of circSlc8a1 
      siRNA or SMC-specific Lamtor1 knockout mice prevented neointimal hyperplasia in 
      vein grafts in vivo. Conclusions: Our study reveals a novel mechanobiological 
      mechanism underlying the dedifferentiation and proliferation of venous SMCs in 
      neointimal hyperplasia. CircSlc81/miR-20a-5p/Lamtor1 axis induced by arterial 
      cyclic stretch may be a potential clinical target that attenuates neointimal 
      hyperplasia in grafted vessels.
CI  - (c) The author(s).
FAU - Liu, Ji-Ting
AU  - Liu JT
AD  - Institute of Mechanobiology & Medical Engineering, School of Life Sciences & 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
FAU - Yao, Qing-Ping
AU  - Yao QP
AD  - Institute of Mechanobiology & Medical Engineering, School of Life Sciences & 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
FAU - Chen, Yi
AU  - Chen Y
AD  - Institute of Mechanobiology & Medical Engineering, School of Life Sciences & 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
FAU - Lv, Fan
AU  - Lv F
AD  - Department of Pediatric Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong 
      University School of Medicine, Shanghai, 200092, China.
FAU - Liu, Ze
AU  - Liu Z
AD  - Institute of Mechanobiology & Medical Engineering, School of Life Sciences & 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
FAU - Bao, Han
AU  - Bao H
AD  - Institute of Mechanobiology & Medical Engineering, School of Life Sciences & 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
FAU - Han, Yue
AU  - Han Y
AD  - Institute of Mechanobiology & Medical Engineering, School of Life Sciences & 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
FAU - Zhang, Ming-Liang
AU  - Zhang ML
AD  - Department of Endocrinology and Metabolism, Shanghai Jiao Tong University 
      Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai 
      Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, 
      Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China.
FAU - Jiang, Zong-Lai
AU  - Jiang ZL
AD  - Institute of Mechanobiology & Medical Engineering, School of Life Sciences & 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
FAU - Qi, Ying-Xin
AU  - Qi YX
AD  - Institute of Mechanobiology & Medical Engineering, School of Life Sciences & 
      Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220621
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
SB  - IM
MH  - Animals
MH  - Cell Proliferation/genetics
MH  - Hyperplasia
MH  - In Situ Hybridization, Fluorescence
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mice
MH  - *MicroRNAs/genetics/metabolism
MH  - *Neointima
MH  - RNA, Small Interfering
PMC - PMC9274756
OTO - NOTNLM
OT  - Lamtor1
OT  - circSlc8a1
OT  - cyclic stretch
OT  - mTORC1
OT  - vein graft
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2022/07/16 06:00
MHDA- 2022/07/19 06:00
PMCR- 2022/01/01
CRDT- 2022/07/15 02:30
PHST- 2021/11/29 00:00 [received]
PHST- 2022/06/03 00:00 [accepted]
PHST- 2022/07/15 02:30 [entrez]
PHST- 2022/07/16 06:00 [pubmed]
PHST- 2022/07/19 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - thnov12p4851 [pii]
AID - 10.7150/thno.69551 [doi]
PST - epublish
SO  - Theranostics. 2022 Jun 21;12(11):4851-4865. doi: 10.7150/thno.69551. eCollection 
      2022.