title: Serum-Sphingosine-1-Phosphate Concentrations Are Inversely Associated with Atherosclerotic Diseases in Humans.
abstract: OBJECTIVE
  Atherosclerotic changes of arteries are the leading cause for deaths in cardiovascular disease and greatly impair patient's quality of life. Sphingosine-1-phosphate (S1P) is a signaling sphingolipid that regulates potentially pro-as well as anti-atherogenic processes. Here, we investigate whether serum-S1P concentrations are associated with peripheral artery disease (PAD) and carotid stenosis (CS).
  
  
  RESULTS
  Serum was sampled from blood donors (controls, N = 174) and from atherosclerotic patients (N = 132) who presented to the hospital with either clinically relevant PAD (N = 102) or CS (N = 30). From all subjects, serum-S1P was measured by mass spectrometry and blood parameters were determined by routine laboratory assays. When compared to controls, atherosclerotic patients before invasive treatment to restore blood flow showed significantly lower serum-S1P levels. This difference cannot be explained by risk factors for atherosclerosis (old age, male gender, hypertension, hypercholesteremia, obesity, diabetes or smoking) or comorbidities (Chronic obstructive pulmonary disease, kidney insufficiency or arrhythmia). Receiver operating characteristic curves suggest that S1P has more power to indicate atherosclerosis (PAD and CS) than high density lipoprotein-cholesterol (HDL-C). In 35 patients, serum-S1P was measured again between one and six months after treatment. In this group, serum-S1P concentrations rose after treatment independent of whether patients had PAD or CS, or whether they underwent open or endovascular surgery. Post-treatment S1P levels were highly associated to platelet numbers measured pre-treatment.
  
  
  CONCLUSIONS
  Our study shows that PAD and CS in humans is associated with decreased serum-S1P concentrations and that S1P may possess higher accuracy to indicate these diseases than HDL-C.
authors.affiliation: Clinic and Polyclinic for Vascular Medicine, University Heart Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Soltau
authors.affiliation: Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Eileen
authors.initials: E
authors.lastname: Mudersbach
authors.affiliation: Clinic and Polyclinic for Vascular Medicine, University Heart Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Geissen
authors.affiliation: Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.affiliation: Center for Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Winkler
authors.affiliation: Institute of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Geffken
authors.affiliation: Institute of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Peine
authors.affiliation: Institute for Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schoen
authors.affiliation: Clinic and Polyclinic for Vascular Medicine, University Heart Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: E Sebastian
authors.initials: ES
authors.lastname: Debus
authors.affiliation: Clinic and Polyclinic for Vascular Medicine, University Heart Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Larena-Avellaneda
authors.affiliation: Clinic and Polyclinic for Vascular Medicine, University Heart Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Guenter
authors.initials: G
authors.lastname: Daum
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D050197:Atherosclerosis / Q000097:blood*; D001777:Blood Coagulation; D016893:Carotid Stenosis / Q000097:blood; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D008246:Lysophospholipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000097:blood; D011379:Prognosis; D012372:ROC Curve; D012044:Regression Analysis; D012307:Risk Factors; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood; D055815:Young Adult
chemical_list: D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine