PMID- 23029186
OWN - NLM
STAT- MEDLINE
DCOM- 20130328
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 9
DP  - 2012
TI  - Role of vegetation-associated protease activity in valve destruction in human 
      infective endocarditis.
PG  - e45695
LID - 10.1371/journal.pone.0045695 [doi]
LID - e45695
AB  - AIMS: Infective endocarditis (IE) is characterized by septic thrombi 
      (vegetations) attached on heart valves, consisting of microbial colonization of 
      the valvular endocardium, that may eventually lead to congestive heart failure or 
      stroke subsequent to systemic embolism. We hypothesized that host defense 
      activation may be directly involved in tissue proteolytic aggression, in addition 
      to pathogenic effects of bacterial colonization. METHODS AND RESULTS: IE valve 
      samples collected during surgery (n = 39) were dissected macroscopically by 
      separating vegetations (VG) and the surrounding damaged part of the valve from 
      the adjacent, apparently normal (N) valvular tissue. Corresponding conditioned 
      media were prepared separately by incubation in culture medium. Histological 
      analysis showed an accumulation of platelets and polymorphonuclear neutrophils 
      (PMNs) at the interface between the VG and the underlying tissue. Apoptotic cells 
      (PMNs and valvular cells) were abundantly detected in this area. Plasminogen 
      activators (PA), including urokinase (uPA) and tissue (tPA) types were also 
      associated with the VG. Secreted matrix metalloproteinase (MMP) 9 was also 
      increased in VG, as was leukocyte elastase and myeloperoxidase (MPO). The 
      presence of neutrophil extracellular traps (NETs) associating MPO and 
      externalized nucleosomes, was shown by immunostaining in the VG. Both MPO and 
      cell-free DNA were released in larger amounts by VG than N samples, suggesting 
      bacterial activation of PMNs within the vegetation. Finally, evidence of 
      proteolytic tissue damage was obtained by the release of fragments of 
      extracellular matrix components such as fibrinogen and fibronectin, as well as 
      protease-sensitive receptors such as the uPA receptor. CONCLUSION: Our data 
      obtained using human IE valves suggest that septic vegetations represent an 
      important source of proteases originating from massive leukocyte recruitment and 
      activation of the host plasminergic system. The latter forms a potential 
      therapeutic target to minimize valvular tissue degradation independently from 
      that induced by bacterial proteases.
FAU - Al-Salih, Ghada
AU  - Al-Salih G
AD  - INSERM U698, Paris, France.
FAU - Al-Attar, Nawwar
AU  - Al-Attar N
FAU - Delbosc, Sandrine
AU  - Delbosc S
FAU - Louedec, Liliane
AU  - Louedec L
FAU - Corvazier, Elisabeth
AU  - Corvazier E
FAU - Loyau, Stephane
AU  - Loyau S
FAU - Michel, Jean-Baptiste
AU  - Michel JB
FAU - Pidard, Dominique
AU  - Pidard D
FAU - Duval, Xavier
AU  - Duval X
FAU - Meilhac, Olivier
AU  - Meilhac O
LA  - eng
PT  - Journal Article
DEP - 20120920
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Culture Media, Conditioned)
RN  - EC 3.4.- (Peptide Hydrolases)
SB  - IM
MH  - Apoptosis
MH  - Blotting, Western
MH  - Culture Media, Conditioned
MH  - Endocarditis/*enzymology/pathology
MH  - Heart Valves/*pathology
MH  - Immunohistochemistry
MH  - Peptide Hydrolases/*metabolism
PMC - PMC3447824
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/10/03 06:00
MHDA- 2013/03/30 06:00
PMCR- 2012/09/20
CRDT- 2012/10/03 06:00
PHST- 2012/02/07 00:00 [received]
PHST- 2012/08/22 00:00 [accepted]
PHST- 2012/10/03 06:00 [entrez]
PHST- 2012/10/03 06:00 [pubmed]
PHST- 2013/03/30 06:00 [medline]
PHST- 2012/09/20 00:00 [pmc-release]
AID - PONE-D-12-04746 [pii]
AID - 10.1371/journal.pone.0045695 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(9):e45695. doi: 10.1371/journal.pone.0045695. Epub 2012 Sep 20.