title: Altered lipidome and antioxidative activity of small, dense HDL in normolipidemic rheumatoid arthritis: relevance of inflammation.
abstract: OBJECTIVE
  High-density lipoprotein (HDL) particles exert potent antiatherogenic activities, including antioxidative actions, which are relevant to attenuation of atherosclerosis progression. Such activities are enriched in small, dense HDL and can be compromised under conditions of chronic inflammation like rheumatoid arthritis (RA). However, structure-function relationships of HDL largely remain indeterminate.
  
  
  METHODS
  The relationships between HDL structure and function were evaluated in normolipidemic patients with active RA (DAS28 > 3.2; n = 12) and in normolipidemic age-matched controls (n = 10). Small, dense HDL3b and 3c particles were isolated from plasma or serum by density gradient ultracentrifugation and their physicochemical characteristics, lipidome (by LC/MS/MS) and antioxidative function (as protection of normolipidemic LDL from free radical-induced oxidation) were evaluated.
  
  
  RESULTS
  As expected, active RA patients featured significantly elevated plasma levels of high-sensitivity C-reactive protein (hsCRP; p < 0.001) and serum amyloid A (SAA; p < 0.01) relative to controls. Antioxidative activity and weight % chemical composition of small, dense HDL did not differ between RA patients and controls (p > 0.05), whereas HDL phosphosphingolipidome was significantly altered in RA. Subgroup analyses revealed that RA patients featuring high levels of inflammation (hsCRP>10 mg/l) possessed small, dense HDL with reduced antioxidative activities (p < 0.01). Furthermore, antioxidative activity of HDL was inversely correlated with plasma hsCRP (p < 0.01).
  
  
  CONCLUSIONS
  These data revealed that (i) despite normolipidemic state, the lipidome of small, dense HDL was altered in RA and (ii) high levels of inflammation can be responsible for the functional deficiency of small, dense HDL in RA.
authors.affiliation: National Institute for Health and Medical Research (INSERM), UMR-ICAN 1166, Paris F-75013, France; Laboratory of Lipids and Lipoproteins, School of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, CONICET, Buenos Aires, Argentina. Electronic address: mulag@hotmail.com.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Gómez Rosso
authors.affiliation: National Institute for Health and Medical Research (INSERM), UMR-ICAN 1166, Paris F-75013, France; Université Pierre et Marie Curie-Paris 6, Paris F-75013 France; AP-HP, Groupe Hospitalier Pitié-Salpétrière, Paris F-75013, France; ICAN, Paris, France. Electronic address: m.lhomme@fondation-ican.com.
authors.forename: Marie
authors.initials: M
authors.lastname: Lhomme
authors.affiliation: Laboratory of Lipids and Lipoproteins, School of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, CONICET, Buenos Aires, Argentina. Electronic address: tomasmero@yahoo.com.ar.
authors.forename: Tomas
authors.initials: T
authors.lastname: Meroño
authors.affiliation: Rheumatology Section, Medical Services and Central Laboratory, Hospital Italiano de Buenos Aires, Instituto Universitario, Escuela de Medicina Hospital Italiano de Buenos Aires, Buenos Aires, Argentina. Electronic address: patricia.sorroche@hospitalitaliano.org.ar.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sorroche
authors.affiliation: Rheumatology Section, Medical Services and Central Laboratory, Hospital Italiano de Buenos Aires, Instituto Universitario, Escuela de Medicina Hospital Italiano de Buenos Aires, Buenos Aires, Argentina. Electronic address: luis.catoggio@hospitalitaliano.org.ar.
authors.forename: Luis
authors.initials: L
authors.lastname: Catoggio
authors.affiliation: Rheumatology Section, Medical Services and Central Laboratory, Hospital Italiano de Buenos Aires, Instituto Universitario, Escuela de Medicina Hospital Italiano de Buenos Aires, Buenos Aires, Argentina. Electronic address: enrique.soriano@hospitalitaliano.org.ar.
authors.forename: Enrique
authors.initials: E
authors.lastname: Soriano
authors.affiliation: Rheumatology Section, Medical Services and Central Laboratory, Hospital Italiano de Buenos Aires, Instituto Universitario, Escuela de Medicina Hospital Italiano de Buenos Aires, Buenos Aires, Argentina. Electronic address: carla.saucedo@hospitalitaliano.org.ar.
authors.forename: Carla
authors.initials: C
authors.lastname: Saucedo
authors.affiliation: Arthritis Service, Hospital de Clínicas "José de San Martín", Buenos Aires, Argentina. Electronic address: vmalah@speedy.com.ar.
authors.forename: Verónica
authors.initials: V
authors.lastname: Malah
authors.affiliation: National Institute for Health and Medical Research (INSERM), UMR-ICAN 1166, Paris F-75013, France; Université Pierre et Marie Curie-Paris 6, Paris F-75013 France; AP-HP, Groupe Hospitalier Pitié-Salpétrière, Paris F-75013, France. Electronic address: carolane.dauteuille@inserm.fr.
authors.forename: Carolane
authors.initials: C
authors.lastname: Dauteuille
authors.affiliation: Laboratory of Lipids and Lipoproteins, School of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, CONICET, Buenos Aires, Argentina. Electronic address: laura.boero@hotmail.com.
authors.forename: Laura
authors.initials: L
authors.lastname: Boero
authors.affiliation: National Institute for Health and Medical Research (INSERM), UMR-ICAN 1166, Paris F-75013, France; Université Pierre et Marie Curie-Paris 6, Paris F-75013 France; AP-HP, Groupe Hospitalier Pitié-Salpétrière, Paris F-75013, France. Electronic address: philippe.lesnik@upmc.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lesnik
authors.affiliation: National Institute for Health and Medical Research (INSERM), UMR-ICAN 1166, Paris F-75013, France; Université Pierre et Marie Curie-Paris 6, Paris F-75013 France; AP-HP, Groupe Hospitalier Pitié-Salpétrière, Paris F-75013, France. Electronic address: junkdna@riseup.net.
authors.forename: Paul
authors.initials: P
authors.lastname: Robillard
authors.affiliation: National Institute for Health and Medical Research (INSERM), UMR-ICAN 1166, Paris F-75013, France; Université Pierre et Marie Curie-Paris 6, Paris F-75013 France; AP-HP, Groupe Hospitalier Pitié-Salpétrière, Paris F-75013, France. Electronic address: john.chapman@upmc.fr.
authors.forename: M
authors.initials: M
authors.lastname: John Chapman
authors.affiliation: Laboratory of Lipids and Lipoproteins, School of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, CONICET, Buenos Aires, Argentina. Electronic address: fdbrites@hotmail.com.
authors.forename: Fernando
authors.initials: F
authors.lastname: Brites
authors.affiliation: National Institute for Health and Medical Research (INSERM), UMR-ICAN 1166, Paris F-75013, France; Université Pierre et Marie Curie-Paris 6, Paris F-75013 France; AP-HP, Groupe Hospitalier Pitié-Salpétrière, Paris F-75013, France. Electronic address: anatol.kontush@upmc.fr.
authors.forename: Anatol
authors.initials: A
authors.lastname: Kontush
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000737:chemistry*; D001172:Arthritis, Rheumatoid / Q000097:blood*; D043303:Aryldialkylphosphatase / Q000097:blood; D002318:Cardiovascular Diseases / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation; D008055:Lipids / Q000097:blood* / Q000737:chemistry; D008074:Lipoproteins / Q000097:blood; D008075:Lipoproteins, HDL / Q000737:chemistry*; D008875:Middle Aged; D018384:Oxidative Stress; D054467:Phospholipases A2 / Q000097:blood; D017698:Postmenopause
chemical_list: D000975:Antioxidants; D008055:Lipids; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D054467:Phospholipases A2; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human
keywords: Antioxidative activity; Cardiovascular disease; Dysfunction; HDL; Inflammation; Rheumatoid arthritis