Chronic Intake of the Selective Serotonin Reuptake Inhibitor Fluoxetine Enhances Atherosclerosis

• DOI: 10.1161/atvbaha.117.310536
• Publication Date: 2018-03-22T09:05:12Z
• Authors: Martina Rami; Raquel Guillamat-...; Petteri Rinne; Melanie Salvermoser; Larisa Ring; Mariaelvy Bianchini; Xavier Blanchet; Remco T.A. Megens; Yvonne Döring; Barbara Walzog; Oliver Soehnlein; Christian Weber; Alexander Faussner; Sabine Steffens
• Keywords: Serotonin reuptake inhibitor; Serotonin Uptake Inhibitors

Cardiovascular diseases and depression are the leading causes of disability in Western countries. Clinical data on potential cardiovascular effects serotonin reuptake inhibitors (SSRIs), most commonly used antidepressant drugs, controversial. In addition to blocking transporter brain, SSRIs deplete major peripheral (5-hydroxytryptamine [5-HT]) storage by inhibiting transporter-mediated uptake platelets. this study, we aimed investigate effect chronic SSRI intake development atherosclerosis.Treatment apolipoprotein E-deficient mice with fluoxetine for 2, 4, or 16 weeks increased atherosclerotic lesion formation, pronounced during early plaque development. Intravital microscopy carotid arteries revealed enhanced myeloid cell adhesion treatment. Mechanistically, found that augmented vascular permeability chemokine-induced integrin-binding activity circulating leukocytes. vitro stimulation murine blood demonstrated fluoxetine, but not 5-HT, could directly promote β1 β2 integrin activation provided C-C motif chemokine ligand 5 was also present. Similar were observed escitalopram. Enhanced 5-induced confirmed a human neutrophil-like line. contrast proatherogenic properties pharmacological inhibition 5-HT synthesizing enzyme tryptophan hydroxylase 1 did atherosclerosis, suggesting occurs independent depletion.SSRI may atherosclerosis therefore potentially increase risk acute events mechanism is depletion.