title: Analytical evaluation of plasma serotonin and sphingosine 1-phosphate and their clinical assessment in early atherosclerosis.
abstract: OBJECTIVE
  Serotonin stored in platelets is released into plasma on aggregation and activation in atherosclerotic diseases. Sphingosine 1-phosphate (S1P) in plasma is mainly derived from red blood cells and is responsible for the production of nitric oxide in endothelial cells and protects vasculature. The purpose of this study was to investigate the plasma levels of serotonin, S1P, and their clinical relationships with vascular endothelial function in patients with early atherosclerosis.
  
  
  METHODS
  Blood was withdrawn from patients with low-to-moderate risks of atherosclerotic diseases (n=49, 39 ± 7 years). Platelet-poor plasma was immediately centrifuged. Serotonin levels in plasma were measured with high-performance liquid chromatography. S1P levels in plasma were measured by high-performance liquid chromatography after fluorescent derivatization with o-phthaldialdehyde. Endothelial function was assessed by endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent dilation was measured by glycerol trinitrate-induced dilation using an ultrasound system.
  
  
  RESULTS
  Plasma serotonin was inversely correlated with the FMD value (r=-0.287, P<0.05). Fourteen patients with dyslipidemia, who had not shown improvements after lifestyle modifications, were subsequently treated with rosuvastatin (2.5 mg/day). After 4 weeks of treatment, rosuvastatin improved lipid profiles. Rosuvastatin increased FMD, whereas glycerol trinitrate-induced dilation was unchanged. Notably, percentage decrease in plasma serotonin was inversely correlated with percentage increase in plasma S1P (r=-0.557, P<0.05).
  
  
  CONCLUSIONS
  Plasma serotonin was inversely correlated with FMD and a decrease in plasma serotonin was inversely correlated with an increase in plasma S1P after statin treatment. The results suggested that plasma levels of serotonin and S1P may be useful for the assessment of endothelial function of patients with low-to-moderate risks of atherosclerotic diseases.
authors.affiliation: Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Tokyo, Japan. tomosugi@med.nagoya-cu.ac.jp
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sugiura
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Dohi
authors.forename: Sumiyo
authors.initials: S
authors.lastname: Yamashita
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ohte
authors.forename: Shiori
authors.initials: S
authors.lastname: Ito
authors.forename: Soichiro
authors.initials: S
authors.lastname: Iwaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hirowatari
authors.forename: Ryunosuke
authors.initials: R
authors.lastname: Ohkawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mishima
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yatomi
authors.forename: Genjiro
authors.initials: G
authors.lastname: Kimura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D004730:Endothelium, Vascular; D005260:Female; D006801:Humans; D008246:Lysophospholipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012701:Serotonin / Q000097:blood*; D017366:Serotonin Receptor Agonists / Q000097:blood*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood; D014664:Vasodilation / Q000502:physiology
chemical_list: D008246:Lysophospholipids; D017366:Serotonin Receptor Agonists; C060506:sphingosine 1-phosphate; D012701:Serotonin; D002784:Cholesterol; D013110:Sphingosine