Chronic Intake of the Selective Serotonin Reuptake Inhibitor Fluoxetine Enhances Atherosclerosis
Chronic Intake of the Selective Serotonin Reuptake Inhibitor Fluoxetine Enhances Atherosclerosis
复制标题
长期摄入选择性血清素再摄取抑制剂氟西汀会加剧动脉粥样硬化
DOI：
10.1161/atvbaha.117.310536
复制
发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Steffens S
中科院分区：
文献类型：
--
作者：
Guillamat-Prats R;Rinne P;Ring L;Söhnlein O;Blanchet X;Megens;Döring Y;Weber C;Faussner A;Steffens S
心血管疾病和抑郁症是西方国家残疾的主要原因。5-羟色胺再摄取抑制剂（SSRIs）是最常用的抗抑郁药物，其潜在心血管效应的临床数据存在争议。除了阻断大脑中的5-羟色胺再摄取转运蛋白外，SSRI还通过抑制血小板中5-羟色胺再摄取转运蛋白介导的摄取来消耗主要的外周5-羟色胺（5-羟色胺[5-HT]）储存。在这项研究中，我们的目的是调查的影响，慢性SSRI摄入量对动脉粥样硬化的发展。方法和结果治疗载脂蛋白E-缺陷的小鼠与SSRI氟西汀2，4，或16周增加动脉粥样硬化病变的形成，在早期斑块的发展最显着的效果。颈动脉活体显微镜检查显示氟西汀治疗后髓样细胞粘附增强。从机制上讲，我们发现氟西汀增加了血管通透性，增加了趋化因子诱导的循环白细胞整合素结合活性。体外刺激小鼠血液表明，氟西汀，而不是5-HT，可以直接促进β1和β2整合素活化，提供C-C基序趋化因子配体5也存在。SSRI艾司西酞普兰也观察到类似的效果。在人嗜酸性粒细胞样细胞系中也证实了氟西汀增强C-C基序趋化因子配体5诱导的整合素活化。在proatherogenic性质的氟西汀，药理学抑制外周5-HT合成酶色氨酸羟化酶1没有促进动脉粥样硬化，这表明proatherogenic作用的氟西汀发生独立的外周5-HT depletion.ConclusionsSSRI摄入量可能会促进动脉粥样硬化，因此可能增加急性心血管事件的风险的机制是独立的5-HT耗尽。
ObjectiveCardiovascular 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 ResultsTreatment 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.ConclusionsSSRI intake may promote atherosclerosis and therefore potentially increase the risk for acute cardiovascular events by a mechanism that is independent of 5-HT depletion.
登录
查看更多内容
影响因子：
20.1
作者：
Drechsler M;de Jong R;Rossaint J;Viola JR;Leoni G;Wang JM;Grommes J;Hinkel R;Kupatt C;Weber C;Döring Y;Zarbock A;Soehnlein O
通讯作者：
Soehnlein O
DOI：
10.1016/0031-6989(85)90067-0
发表时间：
1985-01-01
期刊：
PHARMACOLOGICAL RESEARCH COMMUNICATIONS
影响因子：
--
作者：
VANNUETEN, JM;JANSSENS, WJ;VANHOUTTE, PM
通讯作者：
VANHOUTTE, PM
影响因子：
2.9
作者：
Biffi, A.;Scotti, L.;Corrao, G.
通讯作者：
Corrao, G.
5-羟色胺对人类肠道运动功能的影响。
影响因子：
5.9
作者：
T. Hendrix;M. Atkinson;J. Clifton;F. Ingelfinger
通讯作者：
F. Ingelfinger
影响因子：
37.8
作者：
Ortega-Gomez A;Salvermoser M;Rossaint J;Pick R;Brauner J;Lemnitzer P;Tilgner J;de Jong RJ;Megens RT;Jamasbi J;Döring Y;Pham CT;Scheiermann C;Siess W;Drechsler M;Weber C;Grommes J;Zarbock A;Walzog B;Soehnlein O
通讯作者：
Soehnlein O