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

Lekakis, John; Ikonomidis, Ignatios; Papoutsi, Zoi; Moutsatsou, Paraskevi; Nikolaou, Maria; Parissis, John; Kremastinos, Dimitrios Th.

doi:10.1016/j.ijcard.2008.10.010

« Previous Next »International Journal of Cardiology
Volume 139, Issue 2 , Pages 150-158, 4 March 2010

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

John Lekakis
- 2nd Department of Cardiology, Attikon Hospital, University of Athens, School of Medicine, Athens, Greece
Ignatios Ikonomidis
- 2nd Department of Cardiology, Attikon Hospital, University of Athens, School of Medicine, Athens, Greece
- Corresponding author. 19 Perikleous Str, 14343, Athens, Greece. Tel.: +30 6944805732; fax: +30 210 7299201.
Zoi Papoutsi
- Department of Biological Chemistry, University of Athens, School of Medicine, Athens, Greece
Paraskevi Moutsatsou
- Department of Biological Chemistry, University of Athens, School of Medicine, Athens, Greece
Maria Nikolaou
- 2nd Department of Cardiology, Attikon Hospital, University of Athens, School of Medicine, Athens, Greece
John Parissis
- 2nd Department of Cardiology, Attikon Hospital, University of Athens, School of Medicine, Athens, Greece
Dimitrios Th. Kremastinos
- 2nd Department of Cardiology, Attikon Hospital, University of Athens, School of Medicine, Athens, Greece

Received 14 January 2008; received in revised form 20 September 2008; accepted 12 October 2008. published online 12 November 2008.

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-1and 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 from10⁻⁷ 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).

Conclusion

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.

Keywords: Adhesion molecules, Selective serotonin reuptake inhibitors, Endothelial cells