title: Plasmalogens of high-density lipoproteins (HDL) are associated with coronary artery disease and anti-apoptotic activity of HDL.
abstract: OBJECTIVE
  Low high-density lipoprotein (HDL) cholesterol and loss of atheroprotective functions of HDL are associated with coronary artery disease (CAD). Here, we investigated the associations of HDL phospholipids with acute and stable CAD as well as with the anti-apoptotic activity of HDL.
  
  
  METHODS
  49 species of phosphatidylcholines (PCs), lysophosphatidylcholines and sphingomyelins (SMs) as well as three species of sphingosine-1-phosphate (S1P) were quantified by liquid chromatography - mass spectrometry in HDL isolated from 22 healthy subjects as well as 23 and 22 patients with stable CAD and acute coronary syndrome (ACS), respectively. Native HDL and artificially reconstituted HDL (rHDL) were tested for their capacity to inhibit apoptosis of endothelial cells (ECs) induced by serum deprivation.
  
  
  RESULTS
  HDL of CAD or ACS patients differed from HDL of healthy controls by the content in nine of the 52 quantified phospholipid species as well as reduced anti-apoptotic activity. The capacity of HDL to inhibit EC apoptosis correlated significantly with five of eleven odd-chain PC's (= plasmalogens), two S1P's, SM42:2, PC34:2, and PC32:0. An orthogonal partial least square - discriminant analysis revealed independent associations of stable CAD with HDL-associated PC34:2, PC33:3 and PC35:2 as well as anti-apoptotic activity of HDL and of ACS with HDL-associated PC33:3, PC35:2, SM42:1, PC34:2 and PC36:2. rHDL reconstituted with apoA-I, PC34:1, and PC35:2 inhibited apoptosis of EC's more effectively than rHDL containing only apoA-I and PC34:1.
  
  
  CONCLUSIONS
  The inverse association of HDL-plasmalogen levels with both stable and acute CAD may reflect direct anti-apoptotic effects of plasmologens on ECs.
authors.affiliation: Institute of Clinical Chemistry, University and University Hospital of Zurich, Switzerland; Competence Center for Integrated Human Physiology, University of Zurich, Switzerland.
authors.forename: Iryna
authors.initials: I
authors.lastname: Sutter
authors.affiliation: Institute of Clinical Chemistry, University and University Hospital of Zurich, Switzerland; Competence Center for Integrated Human Physiology, University of Zurich, Switzerland.
authors.forename: Srividya
authors.initials: S
authors.lastname: Velagapudi
authors.affiliation: Institute of Clinical Chemistry, University and University Hospital of Zurich, Switzerland; Competence Center for Personalized Medicine, ETH Zurich and University of Zurich, Switzerland.
authors.forename: Alaa
authors.initials: A
authors.lastname: Othman
authors.affiliation: Division of Nephrology, Institute of Physiology, University of Zurich, Switzerland.
authors.forename: Meliana
authors.initials: M
authors.lastname: Riwanto
authors.affiliation: Divison of Cardiology, University Hospital Zurich, Switzerland; Cardiovascular Research, Institute of Physiology, University of Zurich, Switzerland.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Manz
authors.affiliation: Institute of Clinical Chemistry, University and University Hospital of Zurich, Switzerland; Competence Center for Integrated Human Physiology, University of Zurich, Switzerland.
authors.forename: Lucia
authors.initials: L
authors.lastname: Rohrer
authors.affiliation: Institute of Clinical Chemistry, University and University Hospital of Zurich, Switzerland; Competence Center for Integrated Human Physiology, University of Zurich, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Rentsch
authors.affiliation: Institute of Clinical Chemistry, University and University Hospital of Zurich, Switzerland; Competence Center for Integrated Human Physiology, University of Zurich, Switzerland.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Hornemann
authors.affiliation: Competence Center for Integrated Human Physiology, University of Zurich, Switzerland; Divison of Cardiology, University Hospital Zurich, Switzerland; Cardiovascular Research, Institute of Physiology, University of Zurich, Switzerland.
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
authors.affiliation: Institute of Clinical Chemistry, University and University Hospital of Zurich, Switzerland; Competence Center for Integrated Human Physiology, University of Zurich, Switzerland; Competence Center for Personalized Medicine, ETH Zurich and University of Zurich, Switzerland. Electronic address: arnold.voneckardstein@usz.ch.
authors.forename: Arnold
authors.initials: A
authors.lastname: von Eckardstein
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood; D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000378:metabolism; D017209:Apoptosis; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D003324:Coronary Artery Disease / Q000097:blood*; D016002:Discriminant Analysis; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008055:Lipids; D008075:Lipoproteins, HDL / Q000737:chemistry*; D008244:Lysophosphatidylcholines / Q000737:chemistry; D008246:Lysophospholipids / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000737:chemistry; D010955:Plasmalogens / Q000737:chemistry*; D013109:Sphingomyelins / Q000737:chemistry; D013110:Sphingosine / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D008055:Lipids; D008075:Lipoproteins, HDL; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D010713:Phosphatidylcholines; D010955:Plasmalogens; D013109:Sphingomyelins; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: Apoptosis; Coronary artery disease; Endothelial cells; HDL; Lipidomics; Plasmalogens; Sphingosine-1-phosphate