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.
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.
Lekakis
John
J
2nd Department of Cardiology, Attikon Hospital, University of Athens, School of Medicine, Athens, Greece.
Ikonomidis
Ignatios
I
Papoutsi
Zoi
Z
Moutsatsou
Paraskevi
P
Nikolaou
Maria
M
Parissis
John
J
Kremastinos
Dimitrios Th
DT
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
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