PMID- 35740296
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 10
IP  - 6
DP  - 2022 May 30
TI  - Modulation of Rxralpha Expression in Mononuclear Phagocytes Impacts on Cardiac 
      Remodeling after Ischemia-Reperfusion Injury.
LID - 10.3390/biomedicines10061274 [doi]
LID - 1274
AB  - Retinoid X receptors (RXRs), as members of the steroid/thyroid hormone 
      superfamily of nuclear receptors, are crucial regulators of immune response 
      during health and disease. RXR subtype expression is dependent on tissue and cell 
      type, RXRalpha being the relevant isoform in monocytes and macrophages. Previous 
      studies have assessed different functions of RXRs and positive implications of 
      RXR agonists on outcomes after ischemic injuries have been described. However, 
      the impact of a reduced Rxralpha expression in mononuclear phagocytes on cardiac 
      remodeling after myocardial infarction (MI) has not been investigated to date. 
      Here, we use a temporally controlled deletion of Rxralpha in monocytes and 
      macrophages to determine its role in ischemia-reperfusion injury. We show that 
      reduced expression of Rxralpha in mononuclear phagocytes leads to a decreased 
      phagocytic activity and an accumulation of apoptotic cells in the myocardium, 
      reduces angiogenesis and cardiac macrophage proliferation in the infarct border 
      zone/infarct area, and has an impact on monocyte/macrophage subset composition. 
      These changes are associated with a greater myocardial defect 30 days after 
      ischemia/reperfusion injury. Overall, the reduction of Rxralpha levels in monocytes 
      and macrophages negatively impacts cardiac remodeling after myocardial 
      infarction. Thus, RXRalpha might represent a therapeutic target to regulate the 
      immune response after MI in order to improve cardiac remodeling.
FAU - Rauber, Saskia
AU  - Rauber S
AUID- ORCID: 0000-0001-8901-5572
AD  - Medical Clinic I., Department of Cardiology, University Hospital, Ludwig 
      Maximilian University, 81377 Munich, Germany.
AD  - Department of Neurology, Medical Faculty, Heinrich Heine University of 
      Dusseldorf, 40225 Dusseldorf, Germany.
FAU - Fischer, Maximilian
AU  - Fischer M
AUID- ORCID: 0000-0001-9172-3316
AD  - Medical Clinic I., Department of Cardiology, University Hospital, Ludwig 
      Maximilian University, 81377 Munich, Germany.
FAU - Messerer, Denise
AU  - Messerer D
AD  - Medical Clinic I., Department of Cardiology, University Hospital, Ludwig 
      Maximilian University, 81377 Munich, Germany.
FAU - Wimmler, Vanessa
AU  - Wimmler V
AD  - Medical Clinic I., Department of Cardiology, University Hospital, Ludwig 
      Maximilian University, 81377 Munich, Germany.
FAU - Konda, Kumaraswami
AU  - Konda K
AD  - Medical Clinic I., Department of Cardiology, University Hospital, Ludwig 
      Maximilian University, 81377 Munich, Germany.
FAU - Todica, Andrei
AU  - Todica A
AUID- ORCID: 0000-0003-1504-6565
AD  - Department of Nuclear Medicine, Ludwig Maximilian University, 81377 Munich, 
      Germany.
FAU - Lorenz, Michael
AU  - Lorenz M
AD  - Medical Clinic I., Department of Cardiology, University Hospital, Ludwig 
      Maximilian University, 81377 Munich, Germany.
FAU - Titova, Anna
AU  - Titova A
AD  - Medical Clinic I., Department of Cardiology, University Hospital, Ludwig 
      Maximilian University, 81377 Munich, Germany.
FAU - Schulz, Christian
AU  - Schulz C
AUID- ORCID: 0000-0002-8149-0747
AD  - Medical Clinic I., Department of Cardiology, University Hospital, Ludwig 
      Maximilian University, 81377 Munich, Germany.
AD  - DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart 
      Alliance, 80802 Munich, Germany.
FAU - Weinberger, Tobias
AU  - Weinberger T
AD  - Medical Clinic I., Department of Cardiology, University Hospital, Ludwig 
      Maximilian University, 81377 Munich, Germany.
AD  - DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart 
      Alliance, 80802 Munich, Germany.
LA  - eng
GR  - 81Z0600204/Federal Ministry of Education and Research/
GR  - 81X2600252/Federal Ministry of Education and Research/
GR  - 81X2600256/Federal Ministry of Education and Research/
GR  - no grant number/LMUexcellent/
GR  - no grant number/Friedrich-Baur Stiftung/
GR  - no grant number/Deutsche Stiftung fur Herzforschung/
PT  - Journal Article
DEP - 20220530
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC9219801
OTO - NOTNLM
OT  - inflammation
OT  - ischemia/reperfusion injury
OT  - macrophages
OT  - mononuclear phagocytes
OT  - retinoid receptors
COIS- The authors declare no conflict of interest.
EDAT- 2022/06/25 06:00
MHDA- 2022/06/25 06:01
PMCR- 2022/05/30
CRDT- 2022/06/24 01:05
PHST- 2022/04/25 00:00 [received]
PHST- 2022/05/21 00:00 [revised]
PHST- 2022/05/26 00:00 [accepted]
PHST- 2022/06/24 01:05 [entrez]
PHST- 2022/06/25 06:00 [pubmed]
PHST- 2022/06/25 06:01 [medline]
PHST- 2022/05/30 00:00 [pmc-release]
AID - biomedicines10061274 [pii]
AID - biomedicines-10-01274 [pii]
AID - 10.3390/biomedicines10061274 [doi]
PST - epublish
SO  - Biomedicines. 2022 May 30;10(6):1274. doi: 10.3390/biomedicines10061274.