title: Selective serotonin re-uptake inhibitors decrease the cytokine-induced endothelial adhesion molecule expression, the endothelial adhesiveness to monocytes and the circulating levels of vascular adhesion molecules.
abstract: BACKGROUND
  Selective serotonin reuptake inhibitors (SSRIs) exert cardioprotective effects. We examined whether SSRIs a) modulate endothelial cell expression of vascular cell adhesion molecule (VCAM-1), intracellular adhesion molecule (ICAM-1) and adhesiveness to U937 monocytes, b) reduce the circulating levels of these adhesion molecules in vivo.
  
  
  METHODS
  We assessed the effect of SSRIs, (citalopram, fluvoxamine and fluoxetine), on TNF-alpha-induced expression of VCAM-1 and ICAM-1 in human aorta endothelial cells and adhesiveness to U937 monocytes. Cells were incubated with TNF-alpha in the absence and in the presence of SSRIs concentrations from 10(-7) M to10(-4) M and the VCAM-1 and ICAM-1 expression was quantified by cell-ELISA. The TNF-alpha-stimulated adhesiveness to U937 monocytes was also assessed. Twenty five patients with chronic heart failure and depression were randomized to receive sertaline 50 mg, p.o., o.d. (n=13) or placebo. At baseline and 3-months after treatment, we measured VCAM-1 and ICAM-1 plasma levels.
  
  
  RESULTS
  SSRIs decreased the TNF-alpha-induced endothelial expression of VCAM-1 at concentration range 10(-7) M to 10(-4) M (p<0.05). ICAM-1 expression was decreased in the presence of fluvoxamine and fluoxetine at concentrations from 10(-7) M to 10(-4) M (p<0.05) and in the presence of citalopram at concentrations from 10(-7) M to 10(-5) M (p<0.05). All SSRIs inhibited the TNF-alpha-stimulated adhesiveness to U937 cells at 10(-5) M and 10(-4) M (p<0.05). Compared to baseline, there was a greater reduction in ICAM-1 and VCAM-1 levels post-sertaline than post placebo in heart failure patients (p<0.05).
  
  
  CONCLUSIONS
  SSRIs may exhibit an anti-inflammatory activity on endothelial cells and reduce circulating VCAM-1 and ICAM-1 in vivo, a mechanism which may partly mediate their cardioprotective effects.
authors.affiliation: 2nd Department of Cardiology, Attikon Hospital, University of Athens, School of Medicine, Athens, Greece.
authors.forename: John
authors.initials: J
authors.lastname: Lekakis
authors.forename: Ignatios
authors.initials: I
authors.lastname: Ikonomidis
authors.forename: Zoi
authors.initials: Z
authors.lastname: Papoutsi
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Moutsatsou
authors.forename: Maria
authors.initials: M
authors.lastname: Nikolaou
authors.forename: John
authors.initials: J
authors.lastname: Parissis
authors.forename: Dimitrios Th
authors.initials: DT
authors.lastname: Kremastinos
mesh_terms: D000328:Adult; D000368:Aged; D001011:Aorta / Q000166:cytology; D002448:Cell Adhesion / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002908:Chronic Disease; D015283:Citalopram / Q000494:pharmacology; D003863:Depression / Q000150:complications / Q000188:drug therapy; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005473:Fluoxetine / Q000494:pharmacology; D016666:Fluvoxamine / Q000494:pharmacology; D006333:Heart Failure / Q000150:complications / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D020280:Sertraline / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020298:U937 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D015283:Citalopram; D005473:Fluoxetine; D016666:Fluvoxamine; D018799:Intercellular Adhesion Molecule-1; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1