PMID- 33736980
OWN - NLM
STAT- MEDLINE
DCOM- 20230331
LR  - 20230331
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 168
DP  - 2021 May 20
TI  - Macrophage p47(phox) regulates pressure overload-induced left ventricular 
      remodeling by modulating IL-4/STAT6/PPARgamma signaling.
PG  - 168-179
LID - S0891-5849(21)00159-3 [pii]
LID - 10.1016/j.freeradbiomed.2021.03.007 [doi]
AB  - NADPH oxidase (Nox) mediates ROS production and contributes to cardiac 
      remodeling. However, macrophage p47(phox), a Nox subunit regulating cardiac 
      remodeling, is unclear. We aimed to investigate the role of macrophage p47(phox) 
      in hypertensive cardiac remodeling. Pressure-overload induced by Angiotensin II 
      (AngII) for two weeks in young adult male p47(phox) deficient (KO) mice showed 
      aggravated cardiac dysfunction and hypertrophy as indicated from 
      echocardiographic and histological studies in comparison with wild-type 
      littermates (WT). Additionally, LV of AngII-infused KO mice showed augmented 
      interstitial fibrosis, collagen deposition and, myofibroblasts compared to 
      AngII-infused WT mice. Moreover, these changes in AngII-infused KO mice 
      correlated well with the gene analysis of hypertrophic and fibrotic markers. 
      Similar results were also found in the transverse aortic constriction model. 
      Further, AngII-infused KO mice showed elevated circulating immunokines and 
      increased LV leukocytes infiltration and CD206(+) macrophages compared to 
      AngII-infused WT mice. Likewise, LV of AngII-infused KO mice showed upregulated 
      mRNA expression of anti-inflammatory/pro-fibrotic M2 macrophage markers (Ym1, 
      Arg-1) compared to AngII-infused WT mice. AngII and IL-4 treated bone 
      marrow-derived macrophages (BMDMs) from KO mice showed upregulated M2 macrophage 
      markers and STAT6 phosphorylation (Y641) compared to AngII and IL-4 treated WT 
      BMDMs. These alterations were at least partly mediated by macrophage as bone 
      marrow transplantation from KO mice into WT mice aggravated cardiac remodeling. 
      Mechanistically, AngII-infused KO mice showed hyperactivated IL-4/STAT6/PPARgamma 
      signaling and downregulated SOCS3 expression compared to AngII-infused WT mice. 
      Our studies show that macrophage p47(phox) limits anti-inflammatory signaling and 
      extracellular matrix remodeling in response to pressure-overload.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Reddy, Sukka Santosh
AU  - Reddy SS
AD  - Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, 226031, 
      India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, 
      India.
FAU - Agarwal, Heena
AU  - Agarwal H
AD  - Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, 226031, 
      India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, 
      India.
FAU - Jaiswal, Anant
AU  - Jaiswal A
AD  - Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, 226031, 
      India.
FAU - Jagavelu, Kumaravelu
AU  - Jagavelu K
AD  - Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, 226031, 
      India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, 
      India.
FAU - Dikshit, Madhu
AU  - Dikshit M
AD  - Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, 226031, 
      India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, 
      India.
FAU - Barthwal, Manoj Kumar
AU  - Barthwal MK
AD  - Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, 226031, 
      India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, 
      India. Electronic address: manojbarthwal@cdri.res.in.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210315
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 11128-99-7 (Angiotensin II)
RN  - 207137-56-2 (Interleukin-4)
RN  - 0 (PPAR gamma)
RN  - 0 (Stat6 protein, mouse)
RN  - 0 (STAT6 Transcription Factor)
SB  - IM
MH  - Animals
MH  - Male
MH  - Mice
MH  - Angiotensin II
MH  - Interleukin-4/genetics
MH  - Macrophages
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - *PPAR gamma/genetics
MH  - STAT6 Transcription Factor/genetics
MH  - *Ventricular Remodeling
OTO - NOTNLM
OT  - Angiotensin II
OT  - Fibrosis
OT  - Hypertension
OT  - Hypertrophy
OT  - Macrophages
OT  - p47(phox)
EDAT- 2021/03/20 06:00
MHDA- 2021/06/29 06:00
CRDT- 2021/03/19 06:14
PHST- 2020/12/07 00:00 [received]
PHST- 2021/03/02 00:00 [revised]
PHST- 2021/03/05 00:00 [accepted]
PHST- 2021/03/20 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2021/03/19 06:14 [entrez]
AID - S0891-5849(21)00159-3 [pii]
AID - 10.1016/j.freeradbiomed.2021.03.007 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2021 May 20;168:168-179. doi: 
      10.1016/j.freeradbiomed.2021.03.007. Epub 2021 Mar 15.