Francis O'Neill1, Meliana Riwanto2, Marietta Charakida1, Sophie Colin3, Jasmin Manz2, Eve McLoughlin1, Tauseef Khan1, Nigel Klein4, Christopher W M Kay5, Kalpesh Patel6, Giulia Chinetti3, Bart Staels3, Francesco D'Aiuto6, Ulf Landmesser2, John Deanfield7. 1. National Centre for Cardiovascular Prevention and Outcomes (NCCPO), Institute of Cardiovascular Science, University College London, London, UK. 2. Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland. 3. Université Lille 2, Institut Pasteur de Lille, Inserm UMR1011, EGID, Lille F-59000, France. 4. Infectious Diseases & Microbiology Unit, Institute of Child Health, University College London, London, UK. 5. Institute of Structural & Molecular Biology and London Centre for Nanotechnology, University College London, London, UK. 6. Periodontology Unit, Department of Clinical Research, University College London Eastman Dental Institute, London, UK. 7. 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.
Abstract
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. APPROACH AND 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. CONCLUSION: 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.
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. APPROACH AND 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. CONCLUSION: 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.
Authors: Arthur McCullough; Stephen F Previs; Jaividhya Dasarathy; Kwangwon Lee; Abdullah Osme; Chunki Kim; Serguei Ilchenko; Shuhui W Lorkowski; Jonathan D Smith; Srinivasan Dasarathy; Takhar Kasumov Journal: Am J Physiol Endocrinol Metab Date: 2019-09-10 Impact factor: 4.310
Authors: Nicholas J Woudberg; Sarah Pedretti; Sandrine Lecour; Rainer Schulz; Nicolas Vuilleumier; Richard W James; Miguel A Frias Journal: Front Pharmacol Date: 2018-01-22 Impact factor: 5.810
Authors: Francis O'Neill; Marietta Charakida; Eric Topham; Eve McLoughlin; Neha Patel; Emma Sutill; Christopher W M Kay; Francesco D'Aiuto; Ulf Landmesser; Peter C Taylor; John Deanfield Journal: Heart Date: 2016-11-16 Impact factor: 5.994
Authors: S Contreras-Duarte; P Chen; M Andía; S Uribe; P Irarrázaval; S Kopp; S Kern; G Marsche; D Busso; C Wadsack; A Rigotti Journal: Biol Res Date: 2018-09-15 Impact factor: 5.612