PMID- 35359716
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220402
IS  - 1664-302X (Print)
IS  - 1664-302X (Electronic)
IS  - 1664-302X (Linking)
VI  - 13
DP  - 2022
TI  - Fusobacterium nucleatum Accelerates Atherosclerosis via Macrophage-Driven 
      Aberrant Proinflammatory Response and Lipid Metabolism.
PG  - 798685
LID - 10.3389/fmicb.2022.798685 [doi]
LID - 798685
AB  - Periodontitis, an oral chronic inflammatory disease, is reported to show an 
      association with atherosclerotic vascular disease. Fusobacterium nucleatum is an 
      oral commensal bacterium that is abundantly implicated in various forms of 
      periodontal diseases; however, its role in the pathogenesis of atherosclerosis is 
      unclear. This study aimed to elucidate the underlying pathogenic mechanisms of 
      atherosclerosis induced by F. nucleatum to provide new insight on the prevention 
      and treatment of atherosclerosis. We used an animal model, that is, ApoE(-/-) 
      mice were infected with F. nucleatum by oral gavage, and in vitro co-culture 
      models to assess the pathogenicity of F. nucleatum. The results indicate that F. 
      nucleatum ATCC 25586 invaded aortic tissues and substantially increased the 
      progression of atherosclerotic lesions. In addition, F. nucleatum changed plaque 
      composition into a less-stable phenotype, characterized with increased 
      subcutaneous macrophage infiltration, M1 polarization, lipid deposition, cell 
      apoptosis, and reduced extracellular matrix and collagen content. The serum 
      levels of pro-atherosclerotic factors, such as interleukin (IL)-6, IL-1beta, tumor 
      necrosis factor (TNF)-alpha, monocyte chemoattractant protein-1 (MCP-1), c-reactive 
      protein, and oxidized low-density lipoprotein (ox-LDL) and microRNAs (miR-146a, 
      miR-155, and miR-23b) were considerably increased after F. nucleatum stimulation, 
      whereas HDL-c level was reduced. F. nucleatum induced in vitro macrophage 
      apoptosis in a time- and dose-dependent manner. F. nucleatum facilitated 
      ox-LDL-induced cholesterol phagocytosis and accumulation by regulating the 
      expression of lipid metabolism-related genes (AR-A1, ACAT1, ABCA1, and ABCG1). F. 
      nucleatum further worsened the atherosclerotic plaque microenvironment by 
      considerably increasing the levels of IL-6; IL-1beta; TNF-alpha; MCP-1; and MMP-2, 8, 
      and 9 and by suppressing fibronectin (FN) 1 levels during foam cell formation. 
      This study shows that F. nucleatum ATCC 25586 is implicated in atherosclerosis by 
      causing aberrant activation and lipid metabolism in macrophage.
CI  - Copyright (c) 2022 Zhou, Liu, Wu, Zhao and Wu.
FAU - Zhou, Jieyu
AU  - Zhou J
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
AD  - Department of Periodontics, West China Hospital of Stomatology, Sichuan 
      University, Chengdu, China.
FAU - Liu, Lin
AU  - Liu L
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
AD  - Department of Periodontics, West China Hospital of Stomatology, Sichuan 
      University, Chengdu, China.
FAU - Wu, Peiyao
AU  - Wu P
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
AD  - Department of Periodontics, West China Hospital of Stomatology, Sichuan 
      University, Chengdu, China.
FAU - Zhao, Lei
AU  - Zhao L
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
AD  - Department of Periodontics, West China Hospital of Stomatology, Sichuan 
      University, Chengdu, China.
FAU - Wu, Yafei
AU  - Wu Y
AD  - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral 
      Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
AD  - Department of Periodontics, West China Hospital of Stomatology, Sichuan 
      University, Chengdu, China.
LA  - eng
PT  - Journal Article
DEP - 20220311
PL  - Switzerland
TA  - Front Microbiol
JT  - Frontiers in microbiology
JID - 101548977
PMC - PMC8963492
OTO - NOTNLM
OT  - F. nucleatum
OT  - atherosclerosis
OT  - inflammation
OT  - lipid metabolism
OT  - macrophage
OT  - microRNA
OT  - periodontitis
OT  - polarization
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/02 06:00
MHDA- 2022/04/02 06:01
PMCR- 2022/03/11
CRDT- 2022/04/01 05:12
PHST- 2021/10/20 00:00 [received]
PHST- 2022/02/03 00:00 [accepted]
PHST- 2022/04/01 05:12 [entrez]
PHST- 2022/04/02 06:00 [pubmed]
PHST- 2022/04/02 06:01 [medline]
PHST- 2022/03/11 00:00 [pmc-release]
AID - 10.3389/fmicb.2022.798685 [doi]
PST - epublish
SO  - Front Microbiol. 2022 Mar 11;13:798685. doi: 10.3389/fmicb.2022.798685. 
      eCollection 2022.