PMID- 35536587
OWN - NLM
STAT- MEDLINE
DCOM- 20220512
LR  - 20220716
IS  - 2001-3078 (Electronic)
IS  - 2001-3078 (Linking)
VI  - 11
IP  - 5
DP  - 2022 May
TI  - Extracellular vesicles enclosed-miR-421 suppresses air pollution (PM(2.5) 
      )-induced cardiac dysfunction via ACE2 signalling.
PG  - e12222
LID - 10.1002/jev2.12222 [doi]
LID - e12222
AB  - Air pollution, via ambient PM(2.5,) is a big threat to public health since it 
      associates with increased hospitalisation, incidence rate and  mortality of 
      cardiopulmonary injury. However, the potential mediators of pulmonary injury in 
      PM(2.5) -induced cardiovascular disorder are not fully understood. To investigate 
      a potential cross talk between lung and heart upon PM(2.5) exposure, 
      intratracheal instillation in vivo, organ culture ex vivo and human bronchial 
      epithelial cells (Beas-2B) culture in vitro experiments were performed 
      respectively. The exposed supernatants of Beas-2B were collected to treat primary 
      neonatal rat cardiomyocytes (NRCMs). Upon intratracheal instillation, subacute 
      PM(2.5) exposure caused cardiac dysfunction, which was time-dependent secondary 
      to lung injury in mice, thereby demonstrating a cross-talk between lungs and 
      heart potentially mediated via small extracellular vesicles (sEV). We isolated 
      sEV from PM(2.5) -exposed mice serum and Beas-2B supernatants to analyse the 
      change of sEV subpopulations in response to PM(2.5) . Single particle 
      interferometric reflectance imaging sensing analysis (SP-IRIS) demonstrated that 
      PM(2.5) increased CD63/CD81/CD9 positive particles. Our results indicated that 
      respiratory system-derived sEV containing miR-421 contributed to cardiac 
      dysfunction post-PM(2.5) exposure. Inhibition of miR-421 by AAV9-miR421-sponge 
      could significantly reverse PM(2.5) -induced cardiac dysfunction in mice. We 
      identified that cardiac angiotensin converting enzyme 2 (ACE2) was a downstream 
      target of sEV-miR421, and induced myocardial cell apoptosis and cardiac 
      dysfunction. In addition, we observed that GW4869 (an inhibitor of sEV release) 
      or diminazene aceturate (DIZE, an activator of ACE2) treatment could attenuate 
      PM(2.5) -induced cardiac dysfunction in vivo. Taken together, our results suggest 
      that PM(2.5) exposure promotes sEV-linked miR421 release after lung injury and 
      hereby contributes to PM(2.5) -induced cardiac dysfunction via suppressing ACE2.
CI  - (c) 2022 The Authors. Journal of Extracellular Vesicles published by Wiley 
      Periodicals, LLC on behalf of the International Society for Extracellular 
      Vesicles.
FAU - Wang, Hongyun
AU  - Wang H
AUID- ORCID: 0000-0003-2417-5924
AD  - Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of 
      Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, 
      Shanghai University, Nantong, China.
AD  - Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, 
      Shanghai Engineering Research Center of Organ Repair, School of Life Science, 
      Shanghai University, Shanghai, China.
FAU - Wang, Tianhui
AU  - Wang T
AD  - Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of 
      Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, 
      Shanghai University, Nantong, China.
AD  - Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, 
      Shanghai Engineering Research Center of Organ Repair, School of Life Science, 
      Shanghai University, Shanghai, China.
FAU - Rui, Wei
AU  - Rui W
AD  - Institute for Immunology, Tsinghua University, Beijing, China.
FAU - Xie, Jinxin
AU  - Xie J
AD  - Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of 
      Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, 
      Shanghai University, Nantong, China.
AD  - Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, 
      Shanghai Engineering Research Center of Organ Repair, School of Life Science, 
      Shanghai University, Shanghai, China.
FAU - Xie, Yuling
AU  - Xie Y
AD  - Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of 
      Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, 
      Shanghai University, Nantong, China.
AD  - Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, 
      Shanghai Engineering Research Center of Organ Repair, School of Life Science, 
      Shanghai University, Shanghai, China.
FAU - Zhang, Xiao
AU  - Zhang X
AD  - Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of 
      Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, 
      Shanghai University, Nantong, China.
AD  - Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, 
      Shanghai Engineering Research Center of Organ Repair, School of Life Science, 
      Shanghai University, Shanghai, China.
FAU - Guan, Longfei
AU  - Guan L
AD  - China-America Institute Neuroscience, Beijing Luhe Hospital, Capital Medical 
      University, Beijing, China.
FAU - Li, Guoping
AU  - Li G
AD  - Cardiovascular Division of the Massachusetts General Hospital and Harvard Medical 
      School, Boston, Massachusetts, USA.
FAU - Lei, Zhiyong
AU  - Lei Z
AD  - CDL Research, University Medical Center Utrecht, Utrecht, The Netherlands.
AD  - Department of Cardiology, Laboratory of Experimental Cardiology, University 
      Medical Center Utrecht, Utrecht, The Netherlands.
AD  - UMC Utrecht Regenerative Medicine Center, University Medical Center, Utrecht 
      University, Utrecht, The Netherlands.
FAU - Schiffelers, Raymond M
AU  - Schiffelers RM
AD  - CDL Research, University Medical Center Utrecht, Utrecht, The Netherlands.
FAU - Sluijter, Joost P G
AU  - Sluijter JPG
AD  - Department of Cardiology, Laboratory of Experimental Cardiology, University 
      Medical Center Utrecht, Utrecht, The Netherlands.
AD  - UMC Utrecht Regenerative Medicine Center, University Medical Center, Utrecht 
      University, Utrecht, The Netherlands.
FAU - Xiao, Junjie
AU  - Xiao J
AUID- ORCID: 0000-0002-9202-0003
AD  - Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of 
      Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, 
      Shanghai University, Nantong, China.
AD  - Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, 
      Shanghai Engineering Research Center of Organ Repair, School of Life Science, 
      Shanghai University, Shanghai, China.
LA  - eng
GR  - 2018YFE0113500/National Key Research and Development Project/
GR  - 82020108002/National Natural Science Foundation of China/
GR  - 81911540486/National Natural Science Foundation of China/
GR  - 82000253/National Natural Science Foundation of China/
GR  - 81600008/National Natural Science Foundation of China/
GR  - 20DZ2255400/Science and Technology Commission of Shanghai Municipality/
GR  - 21XD1421300/Science and Technology Commission of Shanghai Municipality/
GR  - 19SG34/the "Dawn" Program of Shanghai Education Commission/
GR  - 20YF1414000/the Sailing Program from Science and Technology Commission of 
      Shanghai/
GR  - 20CG46/"Chenguang Program" of Shanghai Education Development Foundation and 
      Shanghai Municipal Education Commission/
GR  - 725229/Horizon2020 ERC-2016-COG EVICARE/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Extracell Vesicles
JT  - Journal of extracellular vesicles
JID - 101610479
RN  - 0 (MicroRNAs)
RN  - 0 (Particulate Matter)
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
SB  - IM
MH  - *Air Pollution/analysis
MH  - Angiotensin-Converting Enzyme 2
MH  - Animals
MH  - *Extracellular Vesicles
MH  - *Heart Diseases
MH  - *Lung Injury
MH  - Mice
MH  - *MicroRNAs
MH  - Myocytes, Cardiac
MH  - Particulate Matter/adverse effects
MH  - Rats
PMC - PMC9089227
OTO - NOTNLM
OT  - ACE2
OT  - PM2.5
OT  - cardiac dysfunction
OT  - extracellular vesicles
OT  - miR-421
COIS- The authors report no conflict of interest.
EDAT- 2022/05/11 06:00
MHDA- 2022/05/14 06:00
PMCR- 2022/05/10
CRDT- 2022/05/10 11:42
PHST- 2022/04/03 00:00 [revised]
PHST- 2021/10/14 00:00 [received]
PHST- 2022/04/15 00:00 [accepted]
PHST- 2022/05/10 11:42 [entrez]
PHST- 2022/05/11 06:00 [pubmed]
PHST- 2022/05/14 06:00 [medline]
PHST- 2022/05/10 00:00 [pmc-release]
AID - JEV212222 [pii]
AID - 10.1002/jev2.12222 [doi]
PST - ppublish
SO  - J Extracell Vesicles. 2022 May;11(5):e12222. doi: 10.1002/jev2.12222.