PMID- 36049351
OWN - NLM
STAT- MEDLINE
DCOM- 20221021
LR  - 20221207
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 112
DP  - 2022 Nov
TI  - Activation of AMP-activated protein kinase ablated the formation of aortic 
      dissection by suppressing vascular inflammation and phenotypic switching of 
      vascular smooth muscle cells.
PG  - 109177
LID - S1567-5769(22)00661-0 [pii]
LID - 10.1016/j.intimp.2022.109177 [doi]
AB  - BACKGROUND: Aortic dissection (AD) is a fatal vascular disease in absence of 
      effective pharmaceutical therapy. Adenosine monophosphate-activated protein 
      kinase alpha (AMPKalpha) plays a critical role in various cardiovascular diseases. 
      Whether AMPKalpha is involved in the pathogenesis of aortic dissection remains 
      unknown. We aimed to determine whether activation of AMPKalpha prevents the formation 
      of AD. METHODS AND RESULTS: Reduced expression of phosphorylated AMPKalpha (Thr172) 
      and exacerbated phenotypic switching were observed in human aortic tissues from 
      aortic dissection patients compared with those in tissues from controls. In vivo, 
      the formation of aortic dissection in ApoE(-/-) mice was successfully induced by 
      continuous infusion of angiotensin II (AngII) for two weeks, characterized by the 
      activation of vascular inflammation, infiltration of macrophages and phenotypic 
      switching of vascular smooth muscle cells (VSMCs). rAAV2-mediated overexpression 
      of constitutively active AMPKalpha (CA-AMPKalpha) enhanced the expression of 
      phosphorylated AMPKalpha (Thr172) and attenuated AngII-induced occurrence of aortic 
      dissection by suppressing the infiltration of macrophages, activation of vascular 
      inflammation and phenotypic switching of VSMCs. The pathogenesis above was 
      conversely exacerbated by rAAV2-mediated overexpression of dominant negative 
      AMPKalpha2 (DN-AMPKalpha). In vitro, we demonstrated that the administration of an AMPK 
      agonist (AICAR) or transfection of CA-AMPKalpha induced the activation of AMPKalpha and 
      then ameliorated AngII-induced phenotypic switching in the VSMCs and inflammation 
      in the bone marrow-derived macrophages (BMDMs). This could be reversed by the 
      addition of AMPK inhibitor compound C or transfection of DN-AMPKalpha. CONCLUSION: 
      Impaired activation of AMPKalpha may increase the susceptibility to aortic 
      dissection. Our findings verified the protective effects of AMPKalpha on the 
      formation of aortic dissection and may provide evidence for clinical prevention 
      or treatment.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Lei, Lei
AU  - Lei L
AD  - Division of Cardiology, Department of Internal Medicine and Gene Therapy Center, 
      Tongji Hospital, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan 430030, China.
FAU - Zhou, Yanrong
AU  - Zhou Y
AD  - Department of Cardiothoracic Surgery, Tongji Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430030, China.
FAU - Wang, Tiemao
AU  - Wang T
AD  - Division of Cardiology, Department of Internal Medicine and Gene Therapy Center, 
      Tongji Hospital, Tongji Medical College, Huazhong University of Science and 
      Technology, Wuhan 430030, China.
FAU - Zheng, Zhi
AU  - Zheng Z
AD  - Department of Cardiothoracic Surgery, Tongji Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430030, China.
FAU - Chen, Liang
AU  - Chen L
AD  - Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan 430030, China. 
      Electronic address: clg2012tjh@163.com.
FAU - Pan, Youmin
AU  - Pan Y
AD  - Department of Cardiothoracic Surgery, Tongji Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430030, China. Electronic 
      address: panyoumin@126.com.
LA  - eng
PT  - Journal Article
DEP - 20220829
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 415SHH325A (Adenosine Monophosphate)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - 11128-99-7 (Angiotensin II)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Adenosine Monophosphate/pharmacology
MH  - *AMP-Activated Protein Kinases/metabolism
MH  - *Aortic Dissection/metabolism/pathology
MH  - Angiotensin II/metabolism
MH  - Cells, Cultured
MH  - Inflammation/metabolism
MH  - Muscle, Smooth, Vascular
MH  - Myocytes, Smooth Muscle
MH  - Mice, Knockout, ApoE
OTO - NOTNLM
OT  - AMPKalpha
OT  - Aortic dissection
OT  - Inflammation
OT  - Phenotypic switching
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/09/02 06:00
MHDA- 2022/10/21 06:00
CRDT- 2022/09/01 18:21
PHST- 2022/05/13 00:00 [received]
PHST- 2022/08/08 00:00 [revised]
PHST- 2022/08/15 00:00 [accepted]
PHST- 2022/09/02 06:00 [pubmed]
PHST- 2022/10/21 06:00 [medline]
PHST- 2022/09/01 18:21 [entrez]
AID - S1567-5769(22)00661-0 [pii]
AID - 10.1016/j.intimp.2022.109177 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2022 Nov;112:109177. doi: 10.1016/j.intimp.2022.109177. Epub 
      2022 Aug 29.