PMID- 34670018
OWN - NLM
STAT- MEDLINE
DCOM- 20211112
LR  - 20211112
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 35
IP  - 11
DP  - 2021 Nov
TI  - Cytotoxin-associated gene A (CagA) promotes aortic endothelial inflammation and 
      accelerates atherosclerosis through the NLRP3/caspase-1/IL-1beta axis.
PG  - e21942
LID - 10.1096/fj.202100695RR [doi]
AB  - Atherosclerosis is a chronic inflammatory disease. Pathophysiological 
      similarities between chronic infections and atherosclerosis triggered interests 
      between these conditions. The seroepidemiological study showed that Helicobacter 
      pylori strains that express cytotoxin-associated gene A (CagA), an oncoprotein 
      and a major virulence factor, was positively correlated with atherosclerosis and 
      related clinical events. Nevertheless, the underlying mechanism is poorly 
      understood. In this study, the seroprevalence of infection by H. pylori and by 
      strains express CagA assessed by enzyme-linked immunosorbent assay (ELISA) showed 
      that the prevalence of CagA strains rather than H. pylori in patients was 
      positively correlated with atherogenesis. Correspondingly, we found that CagA 
      augmented the growth of plaque of ApoE(-/-) mice in the early stage of 
      atherosclerosis and promoted the expression of adhesion molecules and 
      inflammatory cytokines in mouse aortic endothelial cells (MAECs). 
      Mechanistically, both si-NLRP3 and si-IL-1beta mitigated the promoting effect of 
      CagA on the inflammatory activation of HAECs. In vivo, the inhibition of NLRP3 by 
      MCC950 significantly attenuated the promoting effect of CagA on plaque growth of 
      ApoE(-/-) mice. We also propose NLRP3 as a potential therapeutic target for 
      CagA-positive H. pylori infection-related atherosclerosis and emphasize the 
      importance of inflammation in atherosclerosis pathology.
CI  - (c) 2021 Federation of American Societies for Experimental Biology.
FAU - Li, Bo-Wei
AU  - Li BW
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Liu, Yu
AU  - Liu Y
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Zhang, Lei
AU  - Zhang L
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Guo, Xiao-Qing
AU  - Guo XQ
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Wen, Cheng
AU  - Wen C
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Zhang, Feng
AU  - Zhang F
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Luo, Xue-Ying
AU  - Luo XY
AD  - Affiliated Wuhan Mental Health Center, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Xia, Yuan-Peng
AU  - Xia YP
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Proteins)
RN  - 0 (IL1B protein, mouse)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
RN  - 0 (cagA protein, Helicobacter pylori)
RN  - EC 3.4.22.36 (Casp1 protein, mouse)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Antibodies, Bacterial/blood/immunology
MH  - Antigens, Bacterial/immunology/*metabolism
MH  - Aorta/metabolism/*pathology
MH  - Atherosclerosis/*blood/microbiology
MH  - Bacterial Proteins/immunology/*metabolism
MH  - Caspase 1/*metabolism
MH  - Disease Models, Animal
MH  - Endothelial Cells/*metabolism
MH  - Female
MH  - Helicobacter Infections/*blood/immunology/microbiology
MH  - Helicobacter pylori/immunology/*metabolism
MH  - Humans
MH  - Inflammation/immunology/metabolism
MH  - Interleukin-1beta/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout, ApoE
MH  - Middle Aged
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Plaque, Atherosclerotic/*blood/microbiology
MH  - Seroepidemiologic Studies
MH  - THP-1 Cells
OTO - NOTNLM
OT  - Helicobacter pylori
OT  - CagA
OT  - NLRP3
OT  - atherosclerosis
OT  - endothelial cells
EDAT- 2021/10/21 06:00
MHDA- 2021/11/16 06:00
CRDT- 2021/10/20 17:34
PHST- 2021/08/18 00:00 [revised]
PHST- 2021/04/29 00:00 [received]
PHST- 2021/09/07 00:00 [accepted]
PHST- 2021/10/20 17:34 [entrez]
PHST- 2021/10/21 06:00 [pubmed]
PHST- 2021/11/16 06:00 [medline]
AID - 10.1096/fj.202100695RR [doi]
PST - ppublish
SO  - FASEB J. 2021 Nov;35(11):e21942. doi: 10.1096/fj.202100695RR.