PMID- 32654189
OWN - NLM
STAT- MEDLINE
DCOM- 20210623
LR  - 20220531
IS  - 1399-0012 (Electronic)
IS  - 0902-0063 (Linking)
VI  - 34
IP  - 10
DP  - 2020 Oct
TI  - Targeting the NLRP3 inflammasome to reduce warm ischemic injury in donation after 
      circulatory death heart.
PG  - e14044
LID - 10.1111/ctr.14044 [doi]
AB  - While the donation after circulatory death (DCD) heart transplantation is an 
      emerging clinical practice, the primary source of donor hearts for 
      transplantation remains donation after brain death (DBD) donors. DCD process 
      induces formation of NOD-like receptor family pyrin domain containing-3 (NLRP3) 
      inflammasome, a key mediator of inflammation-driven damage to heart. Inhibition 
      of NLRP3 inflammasome formation could be protective to DCD hearts. Five groups 
      (n = 8 each) of mice were studied-control beating heart donor (CBD) wild-type 
      (WT), DCD WT, CBD NLRP3 knockout (KO), DCD NLRP3 KO, and DCD WT NLRP3 inhibitor 
      group. Hearts were procured and reanimated on a Langendorff system to assess 
      physiologic parameters and then for molecular assays. NLRP3 inhibitor (50 micromol/L) 
      was administered to the DCD-NLRP3 inhibitor group at reanimation. Tissue NLRP3 
      levels were 80% higher in the DCD WT group compared with the CBD-WT group. 
      Caspase-1 activity was significantly elevated in DCD WT but not in KO or NLRP3 
      inhibitor groups. The developed pressures and +/-dP/dt were significantly impaired 
      in the DCD WT group compared with the CBD-WT group, P < .05, but were well 
      preserved in DCD-NLRP3 inhibitor group. The DCD process activates the NLRP3 
      inflammasome, contributing to myocardial damage and dysfunction. NLRP3 
      inflammasome inhibition limits myocardial injury and preserves DCD heart 
      function.
CI  - (c) 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Quader, Mohammed
AU  - Quader M
AUID- ORCID: 0000-0001-8290-043X
AD  - Division of Thoracic and Cardiovascular Surgery, Pauley Heart Center, Virginia 
      Commonwealth University, Richmond, Virginia, USA.
FAU - Mezzaroma, Eleonora
AU  - Mezzaroma E
AD  - School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, USA.
FAU - Kenning, Kristine
AU  - Kenning K
AD  - Division of Thoracic and Cardiovascular Surgery, Pauley Heart Center, Virginia 
      Commonwealth University, Richmond, Virginia, USA.
FAU - Toldo, Stefano
AU  - Toldo S
AUID- ORCID: 0000-0002-1588-4019
AD  - Division of Cardiology, Pauley Heart Center, Virginia Commonwealth University, 
      Richmond, Virginia, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20200802
PL  - Denmark
TA  - Clin Transplant
JT  - Clinical transplantation
JID - 8710240
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Death
MH  - *Heart Transplantation
MH  - Humans
MH  - Inflammasomes
MH  - Mice
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/genetics
MH  - Tissue Donors
MH  - *Tissue and Organ Procurement
OTO - NOTNLM
OT  - Interleukin
OT  - NLRP3
OT  - donation after brain death donor
OT  - donation after circulatory death donor
EDAT- 2020/07/13 06:00
MHDA- 2021/06/24 06:00
CRDT- 2020/07/13 06:00
PHST- 2020/02/11 00:00 [received]
PHST- 2020/06/15 00:00 [revised]
PHST- 2020/07/08 00:00 [accepted]
PHST- 2020/07/13 06:00 [pubmed]
PHST- 2021/06/24 06:00 [medline]
PHST- 2020/07/13 06:00 [entrez]
AID - 10.1111/ctr.14044 [doi]
PST - ppublish
SO  - Clin Transplant. 2020 Oct;34(10):e14044. doi: 10.1111/ctr.14044. Epub 2020 Aug 2.