PMID- 30924864
OWN - NLM
STAT- MEDLINE
DCOM- 20200728
LR  - 20200728
IS  - 1755-3245 (Electronic)
IS  - 0008-6363 (Linking)
VI  - 115
IP  - 13
DP  - 2019 Nov 1
TI  - Long noncoding RNA NEAT1 modulates immune cell functions and is suppressed in 
      early onset myocardial infarction patients.
PG  - 1886-1906
LID - 10.1093/cvr/cvz085 [doi]
AB  - AIMS: Inflammation is a key driver of atherosclerosis and myocardial infarction 
      (MI), and beyond proteins and microRNAs (miRs), long noncoding RNAs (lncRNAs) 
      have been implicated in inflammation control. To obtain further information on 
      the possible role of lncRNAs in the context of atherosclerosis, we obtained 
      comprehensive transcriptome maps of circulating immune cells (peripheral blood 
      mononuclear cells, PBMCs) of early onset MI patients. One lncRNA significantly 
      suppressed in post-MI patients was further investigated in a murine knockout 
      model. METHODS AND RESULTS: Individual RNA-sequencing (RNA-seq) was conducted on 
      PBMCs from 28 post-MI patients with a history of MI at age </=50 years and stable 
      disease >/=3 months before study participation, and from 31 healthy individuals 
      without manifest cardiovascular disease or family history of MI as controls. 
      RNA-seq revealed deregulated protein-coding transcripts and lncRNAs in post-MI 
      PBMCs, among which nuclear enriched abundant transcript (NEAT1) was the most 
      highly expressed lncRNA, and the only one significantly suppressed in patients. 
      Multivariate statistical analysis of validation cohorts of 106 post-MI patients 
      and 85 controls indicated that the PBMC NEAT1 levels were influenced (P = 0.001) 
      by post-MI status independent of statin intake, left ventricular ejection 
      fraction, low-density lipoprotein or high-density lipoprotein cholesterol, or 
      age. We investigated NEAT1-/- mice as a model of NEAT1 deficiency to evaluate if 
      NEAT1 depletion may directly and causally alter immune regulation. RNA-seq of 
      NEAT1-/- splenocytes identified disturbed expression and regulation of 
      chemokines/receptors, innate immunity genes, tumour necrosis factor (TNF) and 
      caspases, and increased production of reactive oxygen species (ROS) under 
      baseline conditions. NEAT1-/- spleen displayed anomalous Treg and TH cell 
      differentiation. NEAT1-/- bone marrow-derived macrophages (BMDMs) displayed 
      altered transcriptomes with disturbed chemokine/chemokine receptor expression, 
      increased baseline phagocytosis (P < 0.0001), and attenuated proliferation 
      (P = 0.0013). NEAT1-/- BMDMs responded to LPS with increased (P < 0.0001) ROS 
      production and disturbed phagocytic activity (P = 0.0318). Monocyte-macrophage 
      differentiation was deregulated in NEAT1-/- bone marrow and blood. NEAT1-/- mice 
      displayed aortic wall CD68+ cell infiltration, and there was evidence of 
      myocardial inflammation which could lead to severe and potentially 
      life-threatening structural damage in some of these animals. CONCLUSION: The 
      study indicates distinctive alterations of lncRNA expression in post-MI patient 
      PBMCs. Regarding the monocyte-enriched NEAT1 suppressed in post-MI patients, the 
      data from NEAT1-/- mice identify NEAT1 as a novel lncRNA-type immunoregulator 
      affecting monocyte-macrophage functions and T cell differentiation. NEAT1 is part 
      of a molecular circuit also involving several chemokines and interleukins 
      persistently deregulated post-MI. Individual profiling of this circuit may 
      contribute to identify high-risk patients likely to benefit from immunomodulatory 
      therapies. It also appears reasonable to look for new therapeutic targets within 
      this circuit.
CI  - Published on behalf of the European Society of Cardiology. All rights reserved. (c) 
      The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.
FAU - Gast, Martina
AU  - Gast M
AD  - Department of Cardiology, Charite-Universitatsmedizin Berlin, Campus Benjamin 
      Franklin, Charite Centrum 11, Hindenburgdamm 30, Berlin, Germany.
FAU - Rauch, Bernhard H
AU  - Rauch BH
AD  - Institute for Pharmacology, Universitatsmedizin Greifswald, 
      Felix-Hausdorff-Strasse 3, Greifswald, Germany.
AD  - German Center for Cardiovascular Research (DZHK), Site Greifswald, 
      Felix-Hausdorff-Strasse 3, Greifswald.
FAU - Haghikia, Arash
AU  - Haghikia A
AD  - Department of Cardiology, Charite-Universitatsmedizin Berlin, Campus Benjamin 
      Franklin, Charite Centrum 11, Hindenburgdamm 30, Berlin, Germany.
AD  - RNA Biology Laboratory, RIKEN Advanced Research Institute, Wako, Saitama, Japan.
FAU - Nakagawa, Shinichi
AU  - Nakagawa S
AD  - RNA Biology Laboratory, RIKEN Advanced Research Institute, Wako, Saitama, Japan.
AD  - Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12 jo, Nishi 
      6-chome, Kita-ku, Sapporo, Japan.
FAU - Haas, Jan
AU  - Haas J
AD  - Department of Cardiology, Institute for Cardiomyopathies, University Hospital 
      Heidelberg, Im Neuenheimer Feld 669, Heidelberg, Germany.
AD  - German Center for Cardiovascular Research (DZHK), Site Heidelberg, Im Neuenheimer 
      Feld 669, Heidelberg, Germany.
FAU - Stroux, Andrea
AU  - Stroux A
AD  - Institute for Biometry and Clinical Epidemiology, Hindenburgdamm 30, Berlin, 
      Germany.
FAU - Schmidt, David
AU  - Schmidt D
AD  - Department of Cardiology, Charite-Universitatsmedizin Berlin, Campus Benjamin 
      Franklin, Charite Centrum 11, Hindenburgdamm 30, Berlin, Germany.
FAU - Schumann, Paul
AU  - Schumann P
AD  - Department of Cardiology, Charite-Universitatsmedizin Berlin, Campus Benjamin 
      Franklin, Charite Centrum 11, Hindenburgdamm 30, Berlin, Germany.
FAU - Weiss, Stefan
AU  - Weiss S
AD  - Interfaculty Institute for Genetics and Functional Genome Research, University of 
      Greifswald, Felix-Hausdorff-Strasse 8, Greifswald, Germany.
FAU - Jensen, Lars
AU  - Jensen L
AD  - Interfaculty Institute for Genetics and Functional Genome Research, University of 
      Greifswald, Felix-Hausdorff-Strasse 8, Greifswald, Germany.
FAU - Kratzer, Adelheid
AU  - Kratzer A
AD  - Department of Cardiology, Charite-Universitatsmedizin Berlin, Campus Benjamin 
      Franklin, Charite Centrum 11, Hindenburgdamm 30, Berlin, Germany.
FAU - Kraenkel, Nicolle
AU  - Kraenkel N
AD  - Department of Cardiology, Charite-Universitatsmedizin Berlin, Campus Benjamin 
      Franklin, Charite Centrum 11, Hindenburgdamm 30, Berlin, Germany.
FAU - Muller, Christian
AU  - Muller C
AD  - Clinic for General and Interventional Cardiology, University Heart Center 
      Hamburg, Martinistrasse 52, Hamburg, Germany.
AD  - German Center for Cardiovascular Research (DZHK), Site Hamburg/Lubeck/Kiel, 
      Martinistrasse 52, Hamburg, Germany.
FAU - Bornigen, Daniela
AU  - Bornigen D
AD  - Clinic for General and Interventional Cardiology, University Heart Center 
      Hamburg, Martinistrasse 52, Hamburg, Germany.
AD  - German Center for Cardiovascular Research (DZHK), Site Hamburg/Lubeck/Kiel, 
      Martinistrasse 52, Hamburg, Germany.
FAU - Hirose, Tetsuro
AU  - Hirose T
AD  - Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
FAU - Blankenberg, Stefan
AU  - Blankenberg S
AD  - Clinic for General and Interventional Cardiology, University Heart Center 
      Hamburg, Martinistrasse 52, Hamburg, Germany.
AD  - German Center for Cardiovascular Research (DZHK), Site Hamburg/Lubeck/Kiel, 
      Martinistrasse 52, Hamburg, Germany.
FAU - Escher, Felicitas
AU  - Escher F
AD  - German Center for Cardiovascular Research (DZHK), Site Berlin, Hindenburgdamm 30, 
      Berlin, Germany.
AD  - Institute of Cardiac Diagnostics and Therapy (IKDT), Hindenburgdamm 30, Berlin, 
      Germany.
AD  - Department of Cardiology CVK, Hindenburgdamm 30, Berlin, Germany.
FAU - Kuhl, Anja A
AU  - Kuhl AA
AD  - iPATH.Berlin-Core Unit Immunopathology, Charite-Universitatsmedizin Berlin, 
      Berlin, Germany.
FAU - Kuss, Andreas W
AU  - Kuss AW
AD  - Interfaculty Institute for Genetics and Functional Genome Research, University of 
      Greifswald, Felix-Hausdorff-Strasse 8, Greifswald, Germany.
FAU - Meder, Benjamin
AU  - Meder B
AD  - Department of Cardiology, Institute for Cardiomyopathies, University Hospital 
      Heidelberg, Im Neuenheimer Feld 669, Heidelberg, Germany.
AD  - German Center for Cardiovascular Research (DZHK), Site Heidelberg, Im Neuenheimer 
      Feld 669, Heidelberg, Germany.
AD  - Department of Genetics, Genome Technology Center, Stanford University Medical 
      School, Stanford, CA, USA.
FAU - Landmesser, Ulf
AU  - Landmesser U
AD  - Department of Cardiology, Charite-Universitatsmedizin Berlin, Campus Benjamin 
      Franklin, Charite Centrum 11, Hindenburgdamm 30, Berlin, Germany.
AD  - German Center for Cardiovascular Research (DZHK), Site Berlin, Hindenburgdamm 30, 
      Berlin, Germany.
AD  - Berlin Institute of Health (BIH), Anna-Louisa-Karsch-Strasse 2, Berlin, Germany.
FAU - Zeller, Tanja
AU  - Zeller T
AD  - Clinic for General and Interventional Cardiology, University Heart Center 
      Hamburg, Martinistrasse 52, Hamburg, Germany.
AD  - German Center for Cardiovascular Research (DZHK), Site Hamburg/Lubeck/Kiel, 
      Martinistrasse 52, Hamburg, Germany.
FAU - Poller, Wolfgang
AU  - Poller W
AD  - Department of Cardiology, Charite-Universitatsmedizin Berlin, Campus Benjamin 
      Franklin, Charite Centrum 11, Hindenburgdamm 30, Berlin, Germany.
AD  - German Center for Cardiovascular Research (DZHK), Site Berlin, Hindenburgdamm 30, 
      Berlin, Germany.
AD  - Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Hindenburgdamm 30, 
      Berlin, Germany.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Chemokines)
RN  - 0 (NEAT1 long non-coding RNA, human)
RN  - 0 (NEAT1 long non-coding RNA, mouse)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (Reactive Oxygen Species)
SB  - IM
CIN - Cardiovasc Res. 2019 Nov 1;115(13):1813-1814. PMID: 31179492
MH  - Adult
MH  - Age of Onset
MH  - Animals
MH  - Case-Control Studies
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Chemokines/genetics/metabolism
MH  - Down-Regulation
MH  - Female
MH  - Humans
MH  - *Immunity, Innate
MH  - Leukocytes, Mononuclear/immunology/*metabolism
MH  - Macrophages/immunology/metabolism
MH  - Male
MH  - Mice, Knockout
MH  - Middle Aged
MH  - Myocardial Infarction/genetics/immunology/*metabolism
MH  - RNA, Long Noncoding/genetics/immunology/*metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction
MH  - Spleen/immunology/metabolism
MH  - T-Lymphocytes, Helper-Inducer/immunology/metabolism
MH  - T-Lymphocytes, Regulatory/immunology/metabolism
MH  - Time Factors
OTO - NOTNLM
OT  - Cardiovascular innate immunity
OT  - Early myocardial infarction
OT  - Immunoregulatory genes
OT  - Long noncoding RNA
OT  - Pattern recognition receptors
EDAT- 2019/03/30 06:00
MHDA- 2020/07/29 06:00
CRDT- 2019/03/30 06:00
PHST- 2018/06/15 00:00 [received]
PHST- 2019/02/15 00:00 [revised]
PHST- 2019/03/27 00:00 [accepted]
PHST- 2019/03/30 06:00 [pubmed]
PHST- 2020/07/29 06:00 [medline]
PHST- 2019/03/30 06:00 [entrez]
AID - 5423185 [pii]
AID - 10.1093/cvr/cvz085 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2019 Nov 1;115(13):1886-1906. doi: 10.1093/cvr/cvz085.