title: Defective functionality of small, dense HDL3 subpopulations in ST segment elevation myocardial infarction: Relevance of enrichment in lysophosphatidylcholine, phosphatidic acid and serum amyloid A.
abstract: BACKGROUND
  Low plasma levels of high-density lipoprotein-cholesterol (HDL-C) are typical of acute myocardial infarction (MI) and predict risk of recurrent cardiovascular events. The potential relationships between modifications in the molecular composition and the functionality of HDL subpopulations in acute MI however remain indeterminate.
  
  
  RESULTS
  ST segment elevation MI (STEMI) patients were recruited within 24h after diagnosis (n=16) and featured low HDL-C (-31%, p<0.05) and acute-phase inflammation (determined as marked elevations in C-reactive protein, serum amyloid A (SAA) and interleukin-6) as compared to age- and sex-matched controls (n=10). STEMI plasma HDL and its subpopulations (HDL2b, 2a, 3a, 3b, 3c) displayed attenuated cholesterol efflux capacity from THP-1 cells (up to -32%, p<0.01, on a unit phospholipid mass basis) vs.
  
  
  METHODS
  Plasma HDL and small, dense HDL3b and 3c subpopulations from STEMI patients exhibited reduced anti-oxidative activity (up to -68%, p<0.05, on a unit HDL mass basis). HDL subpopulations in STEMI were enriched in two proinflammatory bioactive lipids, lysophosphatidylcholine (up to 3.0-fold, p<0.05) and phosphatidic acid (up to 8.4-fold, p<0.05), depleted in apolipoprotein A-I (up to -23%, p<0.05) and enriched in SAA (up to +10.2-fold, p<0.05); such changes were most marked in the HDL3b subfraction. In vitro HDL enrichment in both lysophosphatidylcholine and phosphatidic acid exerted deleterious effects on HDL functionality.
  
  
  CONCLUSIONS
  In the early phase of STEMI, HDL particle subpopulations display marked, concomitant alterations in both lipidome and proteome which are implicated in impaired HDL functionality. Such modifications may act synergistically to confer novel deleterious biological activities to STEMI HDL.
  
  
  CONCLUSIONS
  Our present data highlight complex changes in the molecular composition and functionality of HDL particle subpopulations in the acute phase of STEMI, and for the first time, reveal that concomitant modifications in both the lipidome and proteome contribute to functional deficiencies in cholesterol efflux and antioxidative activities of HDL particles. These findings may provide new biomarkers and new insights in therapeutic strategy to reduce cardiovascular risk in this clinical setting where such net deficiency in HDL function, multiplied by low circulating HDL concentrations, can be expected to contribute to accelerated atherogenesis.
authors.affiliation: National Institute of Health and Medical Research (INSERM), UMR-ICAN 1166, University of Pierre and Marie Curie - Paris 6; Pitié-Salpétrière University Hospital, ICAN, Paris, France; Heart Institute-InCor, University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Rached
authors.affiliation: National Institute of Health and Medical Research (INSERM), UMR-ICAN 1166, University of Pierre and Marie Curie - Paris 6; Pitié-Salpétrière University Hospital, ICAN, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Lhomme
authors.affiliation: National Institute of Health and Medical Research (INSERM), UMR-ICAN 1166, University of Pierre and Marie Curie - Paris 6; Pitié-Salpétrière University Hospital, ICAN, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Camont
authors.affiliation: Heart Institute-InCor, University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gomes
authors.affiliation: National Institute of Health and Medical Research (INSERM), UMR-ICAN 1166, University of Pierre and Marie Curie - Paris 6; Pitié-Salpétrière University Hospital, ICAN, Paris, France.
authors.forename: Carolane
authors.initials: C
authors.lastname: Dauteuille
authors.affiliation: National Institute of Health and Medical Research (INSERM), UMR-ICAN 1166, University of Pierre and Marie Curie - Paris 6; Pitié-Salpétrière University Hospital, ICAN, Paris, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Robillard
authors.affiliation: Heart Institute-InCor, University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil.
authors.forename: Raul D
authors.initials: RD
authors.lastname: Santos
authors.affiliation: National Institute of Health and Medical Research (INSERM), UMR-ICAN 1166, University of Pierre and Marie Curie - Paris 6; Pitié-Salpétrière University Hospital, ICAN, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lesnik
authors.affiliation: Heart Institute-InCor, University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil.
authors.forename: Carlos V
authors.initials: CV
authors.lastname: Serrano
authors.affiliation: National Institute of Health and Medical Research (INSERM), UMR-ICAN 1166, University of Pierre and Marie Curie - Paris 6; Pitié-Salpétrière University Hospital, ICAN, Paris, France.
authors.forename: M John
authors.initials: MJ
authors.lastname: Chapman
authors.affiliation: National Institute of Health and Medical Research (INSERM), UMR-ICAN 1166, University of Pierre and Marie Curie - Paris 6; Pitié-Salpétrière University Hospital, ICAN, Paris, France. Electronic address: anatol.kontush@upmc.fr.
authors.forename: Anatol
authors.initials: A
authors.lastname: Kontush
mesh_terms: D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D002460:Cell Line; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D053440:Lipoproteins, HDL3 / Q000097:blood* / Q000737:chemistry; D008244:Lysophosphatidylcholines / Q000097:blood* / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009203:Myocardial Infarction / Q000097:blood* / Q000473:pathology; D010712:Phosphatidic Acids / Q000097:blood* / Q000737:chemistry; D020543:Proteome / Q000737:chemistry / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; C508600:IL6 protein, human; D015850:Interleukin-6; D053440:Lipoproteins, HDL3; D008244:Lysophosphatidylcholines; D010712:Phosphatidic Acids; D020543:Proteome; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein
keywords: Acute myocardial infarction; Antioxidative activity; Cholesterol efflux; HDL; Inflammation; Lipidomics