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Bacteria in the Adventitia of Cardiovascular Disease Patients with and without Rheumatoid Arthritis.

Curran, Samuel A ; Hollan, Ivana ; Erridge, Clett ; Lappin, David F ; Murray, Colin A ; Sturfelt, Gunnar LU ; Mikkelsen, Knut ; Førre, Oystein T ; Almdahl, Sven M and Fagerhol, Magne K , et al. (2014) In PLoS ONE 9(5).
Abstract
The incidence of atherosclerosis is significantly increased in rheumatoid arthritis (RA). Infection is one factor that may be involved in the pathogenesis of both diseases. The cause of RA and atherosclerosis is unknown, and infection is one of the factors that may be involved in the pathogenesis of both diseases. The aims of this study were to identify bacteria in the aortic adventitia of patients with cardiovascular disease (CVD) in the presence and absence of RA, and to determine the effect of identified candidate pathogens on Toll-like receptor (TLR)-dependent signalling and the proinflammatory response. The aortic adventitia of 11 CVD patients with RA (RA+CVD) and 11 CVD patients without RA (CVD) were collected during coronary artery... (More)
The incidence of atherosclerosis is significantly increased in rheumatoid arthritis (RA). Infection is one factor that may be involved in the pathogenesis of both diseases. The cause of RA and atherosclerosis is unknown, and infection is one of the factors that may be involved in the pathogenesis of both diseases. The aims of this study were to identify bacteria in the aortic adventitia of patients with cardiovascular disease (CVD) in the presence and absence of RA, and to determine the effect of identified candidate pathogens on Toll-like receptor (TLR)-dependent signalling and the proinflammatory response. The aortic adventitia of 11 CVD patients with RA (RA+CVD) and 11 CVD patients without RA (CVD) were collected during coronary artery bypass graft surgery. Bacteria were detected in four samples from CVD patients and three samples from RA+CVD patients and identified by 16S rRNA gene sequencing. Methylobacterium oryzae was identified in all three RA+CVD samples, representing 44.1% of the bacterial flora. The effect of M. oryzae on TLR-dependent signalling was determined by transfection of HEK-293 cells. Although mild TLR2 signalling was observed, TLR4 was insensitive to M. oryzae. Human primary macrophages were infected with M. oryzae, and a TLDA qPCR array targeting 90 genes involved in inflammation and immune regulation was used to profile the transcriptional response. A significant proinflammatory response was observed, with many of the up-regulated genes encoding proinflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α) and chemokines (CCR7, IL-8). The aortic adventitia of CVD patients contains a wide range of bacterial species, and the bacterial flora is significantly less diverse in RA+CVD than CVD patients. M. oryzae may stimulate an proinflammatory response that may aggravate and perpetuate the pathological processes underlying atherosclerosis in RA patients. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
9
issue
5
article number
e98627
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:24874661
  • wos:000336790800053
  • scopus:84902191960
  • pmid:24874661
ISSN
1932-6203
DOI
10.1371/journal.pone.0098627
language
English
LU publication?
yes
id
f181f513-e5a2-4171-a5b5-c5dfc84f0ace (old id 4452356)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24874661?dopt=Abstract
date added to LUP
2016-04-01 13:52:21
date last changed
2022-02-11 23:32:45
@article{f181f513-e5a2-4171-a5b5-c5dfc84f0ace,
  abstract     = {{The incidence of atherosclerosis is significantly increased in rheumatoid arthritis (RA). Infection is one factor that may be involved in the pathogenesis of both diseases. The cause of RA and atherosclerosis is unknown, and infection is one of the factors that may be involved in the pathogenesis of both diseases. The aims of this study were to identify bacteria in the aortic adventitia of patients with cardiovascular disease (CVD) in the presence and absence of RA, and to determine the effect of identified candidate pathogens on Toll-like receptor (TLR)-dependent signalling and the proinflammatory response. The aortic adventitia of 11 CVD patients with RA (RA+CVD) and 11 CVD patients without RA (CVD) were collected during coronary artery bypass graft surgery. Bacteria were detected in four samples from CVD patients and three samples from RA+CVD patients and identified by 16S rRNA gene sequencing. Methylobacterium oryzae was identified in all three RA+CVD samples, representing 44.1% of the bacterial flora. The effect of M. oryzae on TLR-dependent signalling was determined by transfection of HEK-293 cells. Although mild TLR2 signalling was observed, TLR4 was insensitive to M. oryzae. Human primary macrophages were infected with M. oryzae, and a TLDA qPCR array targeting 90 genes involved in inflammation and immune regulation was used to profile the transcriptional response. A significant proinflammatory response was observed, with many of the up-regulated genes encoding proinflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α) and chemokines (CCR7, IL-8). The aortic adventitia of CVD patients contains a wide range of bacterial species, and the bacterial flora is significantly less diverse in RA+CVD than CVD patients. M. oryzae may stimulate an proinflammatory response that may aggravate and perpetuate the pathological processes underlying atherosclerosis in RA patients.}},
  author       = {{Curran, Samuel A and Hollan, Ivana and Erridge, Clett and Lappin, David F and Murray, Colin A and Sturfelt, Gunnar and Mikkelsen, Knut and Førre, Oystein T and Almdahl, Sven M and Fagerhol, Magne K and Goodyear, Carl S and Riggio, Marcello P}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{5}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Bacteria in the Adventitia of Cardiovascular Disease Patients with and without Rheumatoid Arthritis.}},
  url          = {{https://lup.lub.lu.se/search/files/3637806/4986315.pdf}},
  doi          = {{10.1371/journal.pone.0098627}},
  volume       = {{9}},
  year         = {{2014}},
}