We have located links that may give you full text access.
JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Chronic Intake of the Selective Serotonin Reuptake Inhibitor Fluoxetine Enhances Atherosclerosis.
OBJECTIVE: Cardiovascular diseases and depression are the leading causes of disability in Western countries. Clinical data on potential cardiovascular effects of serotonin reuptake inhibitors (SSRIs), the most commonly used antidepressant drugs, are controversial. In addition to blocking serotonin reuptake transporter in the brain, SSRIs deplete the major peripheral serotonin (5-hydroxytryptamine [5-HT]) storage by inhibiting serotonin reuptake transporter-mediated uptake in platelets. In this study, we aimed to investigate the effect of chronic SSRI intake on the development of atherosclerosis.
APPROACH AND RESULTS: Treatment of apolipoprotein E-deficient mice with the SSRI fluoxetine for 2, 4, or 16 weeks increased atherosclerotic lesion formation, with most pronounced effect during early plaque development. Intravital microscopy of carotid arteries revealed enhanced myeloid cell adhesion on fluoxetine treatment. Mechanistically, we found that fluoxetine augmented vascular permeability and increased chemokine-induced integrin-binding activity of circulating leukocytes. In vitro stimulation of murine blood demonstrated that fluoxetine, but not 5-HT, could directly promote β1 and β2 integrin activation provided C-C motif chemokine ligand 5 was also present. Similar effects were observed with the SSRI escitalopram. Enhanced C-C motif chemokine ligand 5-induced integrin activation by fluoxetine was also confirmed in a human neutrophil-like cell line. In contrast to the proatherogenic properties of fluoxetine, pharmacological inhibition of the peripheral 5-HT synthesizing enzyme tryptophan hydroxylase 1 did not promote atherosclerosis, suggesting that the proatherogenic effect of fluoxetine occurs independent of peripheral 5-HT depletion.
CONCLUSIONS: SSRI intake may promote atherosclerosis and therefore potentially increase the risk for acute cardiovascular events by a mechanism that is independent of 5-HT depletion.
APPROACH AND RESULTS: Treatment of apolipoprotein E-deficient mice with the SSRI fluoxetine for 2, 4, or 16 weeks increased atherosclerotic lesion formation, with most pronounced effect during early plaque development. Intravital microscopy of carotid arteries revealed enhanced myeloid cell adhesion on fluoxetine treatment. Mechanistically, we found that fluoxetine augmented vascular permeability and increased chemokine-induced integrin-binding activity of circulating leukocytes. In vitro stimulation of murine blood demonstrated that fluoxetine, but not 5-HT, could directly promote β1 and β2 integrin activation provided C-C motif chemokine ligand 5 was also present. Similar effects were observed with the SSRI escitalopram. Enhanced C-C motif chemokine ligand 5-induced integrin activation by fluoxetine was also confirmed in a human neutrophil-like cell line. In contrast to the proatherogenic properties of fluoxetine, pharmacological inhibition of the peripheral 5-HT synthesizing enzyme tryptophan hydroxylase 1 did not promote atherosclerosis, suggesting that the proatherogenic effect of fluoxetine occurs independent of peripheral 5-HT depletion.
CONCLUSIONS: SSRI intake may promote atherosclerosis and therefore potentially increase the risk for acute cardiovascular events by a mechanism that is independent of 5-HT depletion.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app