Structural and functional changes in HDL with low grade and chronic inflammation.
OBJECTIVE
HDL functionality has been shown to be impaired in inflammatory conditions, including coronary artery disease. The present study aims to determine the impact of low grade and acute inflammation on HDL function and structure.


RESULTS
i) The endothelial protective effects of HDL were compared between 26 periodontal patients and 26 age and sex matched controls by measuring paraoxonase activity in serum and nitric oxide bioavailability and superoxide production in endothelial cells. Paraoxonase activity and nitric oxide bioavailability were reduced, while superoxide production was increased (p<0.01) in periodontal patients compared to controls. ii) HDL function, including cholesterol efflux and vascular cell adhesion molecule-1 expression, was subsequently measured in the periodontal patients following an inflammatory stimulus. There was an acute deterioration in HDL's endothelial protective function, without change in cholesterol efflux, after 24h (p<0.01 for all). These functional changes tracked increases of inflammatory markers and altered HDL composition. Finally, HDL function returned to baseline levels after resolution of inflammation.


CONCLUSIONS
This study demonstrates that even minor alterations in systemic inflammation can impair the endothelial protective effects of HDL. These functional changes were independent of cholesterol efflux and were associated with remodeling of the HDL proteome. All measures of HDL's endothelial protective functions recovered with resolution of inflammation. These findings suggest that HDL dysfunction may represent a novel mechanism linking inflammation with progression of atheroma.
National Centre for Cardiovascular Prevention and Outcomes (NCCPO), Institute of Cardiovascular Science, University College London, London, UK.
Francis
F
O'Neill
Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland.
Meliana
M
Riwanto
National Centre for Cardiovascular Prevention and Outcomes (NCCPO), Institute of Cardiovascular Science, University College London, London, UK.
Marietta
M
Charakida
Université Lille 2, Institut Pasteur de Lille, Inserm UMR1011, EGID, Lille F-59000, France.
Sophie
S
Colin
Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland.
Jasmin
J
Manz
National Centre for Cardiovascular Prevention and Outcomes (NCCPO), Institute of Cardiovascular Science, University College London, London, UK.
Eve
E
McLoughlin
National Centre for Cardiovascular Prevention and Outcomes (NCCPO), Institute of Cardiovascular Science, University College London, London, UK.
Tauseef
T
Khan
Infectious Diseases & Microbiology Unit, Institute of Child Health, University College London, London, UK.
Nigel
N
Klein
Institute of Structural & Molecular Biology and London Centre for Nanotechnology, University College London, London, UK.
Christopher W M
CW
Kay
Periodontology Unit, Department of Clinical Research, University College London Eastman Dental Institute, London, UK.
Kalpesh
K
Patel
Université Lille 2, Institut Pasteur de Lille, Inserm UMR1011, EGID, Lille F-59000, France.
Giulia
G
Chinetti
Université Lille 2, Institut Pasteur de Lille, Inserm UMR1011, EGID, Lille F-59000, France.
Bart
B
Staels
Periodontology Unit, Department of Clinical Research, University College London Eastman Dental Institute, London, UK.
Francesco
F
D'Aiuto
Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland.
Ulf
U
Landmesser
National Centre for Cardiovascular Prevention and Outcomes (NCCPO), Institute of Cardiovascular Science, University College London, London, UK; National Institute for Cardiovascular Outcomes Research, University College London, London, UK. Electronic address: j.deanfield@ucl.ac.uk.
John
J
Deanfield
D000328:Adult; D043303:Aryldialkylphosphatase / Q000378:metabolism*; D016022:Case-Control Studies; D002908:Chronic Disease; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D010518:Periodontitis / Q000097:blood* / Q000503:physiopathology*; D012720:Severity of Illness Index; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D018836:Inflammation Mediators; D008075:Lipoproteins, HDL; D019010:Vascular Cell Adhesion Molecule-1; D009569:Nitric Oxide; D043303:Aryldialkylphosphatase
Atherosclerosis; High-density lipoprotein; Inflammation