title: Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures.
abstract: We previously reported that high density lipoprotein (HDL) protects against the oxidative modification of low density lipoprotein (LDL) induced by artery wall cells causing these cells to produce pro-inflammatory molecules. We also reported that enzyme systems associated with HDL were responsible for this anti-inflammatory property of HDL. We now report studies comparing HDL before and during an acute phase response (APR) in both humans and a croton oil rabbit model. In rabbits, from the onset of APR the protective effect of HDL progressively decreased and was completely lost by day three. As serum amyloid A (SAA) levels in acute phase HDL (AP-HDL) increased, apo A-I levels decreased 73%. Concomitantly, paraoxonase (PON) and platelet activating factor acetylhydrolase (PAF-AH) levels in HDL declined 71 and 90%, respectively, from days one to three. After day three, there was some recovery of the protective effect of HDL. AP-HDL from human patients and rabbits but not normal or control HDL (C-HDL) exhibited increases in ceruloplasmin (CP). This increase in CP was not seen in acute phase VLDL or LDL. C-HDL incubated with purified CP and re-isolated (CP-HDL), lost its ability to inhibit LDL oxidation. Northern blot analyses demonstrated enhanced expression of MCP-1 in coculture cells treated with AP-HDL and CP-HDL compared to C-HDL. Enrichment of human AP-HDL with purified PON or PAF-AH rendered AP-HDL protective against LDL modification. We conclude that under basal conditions HDL serves an anti-inflammatory role but during APR displacement and/or exchange of proteins associated with HDL results in a pro-inflammatory molecule.
authors.affiliation: Department of Medicine, University of California Los Angeles, 90095, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Van Lenten
authors.forename: S Y
authors.initials: SY
authors.lastname: Hama
authors.forename: F C
authors.initials: FC
authors.lastname: de Beer
authors.forename: D M
authors.initials: DM
authors.lastname: Stafforini
authors.forename: T M
authors.initials: TM
authors.lastname: McIntyre
authors.forename: S M
authors.initials: SM
authors.lastname: Prescott
authors.forename: B N
authors.initials: BN
authors.lastname: La Du
authors.forename: A M
authors.initials: AM
authors.lastname: Fogelman
authors.forename: M
authors.initials: M
authors.lastname: Navab
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001011:Aorta / Q000166:cytology / Q000502:physiology; D043303:Aryldialkylphosphatase; D001483:Base Sequence; D002448:Cell Adhesion; D002478:Cells, Cultured; D002570:Ceruloplasmin / Q000096:biosynthesis; D018932:Chemokine CCL2 / Q000096:biosynthesis; D018920:Coculture Techniques; D003436:Croton Oil; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004950:Esterases / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D008075:Lipoproteins, HDL / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D010741:Phospholipases A / Q000378:metabolism; D011817:Rabbits
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018932:Chemokine CCL2; D017931:DNA Primers; D008075:Lipoproteins, HDL; D003436:Croton Oil; D002570:Ceruloplasmin; D004950:Esterases; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D043303:Aryldialkylphosphatase