选择性 5-羟色胺再摄取抑制剂可降低细胞因子诱导的内皮黏附分子表达、内皮细胞对单核细胞的黏附性和血管黏附分子的循环水平。

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.

机构信息

2nd Department of Cardiology, Attikon Hospital, University of Athens, School of Medicine, Athens, Greece.

出版信息

Int J Cardiol. 2010 Mar 4;139(2):150-8. doi: 10.1016/j.ijcard.2008.10.010. Epub 2008 Nov 11.

DOI:10.1016/j.ijcard.2008.10.010

PMID:19004511

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-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).

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.

摘要

背景

选择性 5-羟色胺再摄取抑制剂（SSRIs）具有心脏保护作用。我们研究了 SSRIs 是否 a）调节血管细胞黏附分子（VCAM-1）、细胞间黏附分子（ICAM-1）在人主动脉内皮细胞中的表达和与 U937 单核细胞的黏附性，b）降低这些黏附分子在体内的循环水平。

方法

我们评估了 SSRIs（西酞普兰、氟伏沙明和氟西汀）对 TNF-α诱导的人主动脉内皮细胞 VCAM-1 和 ICAM-1 表达的影响，以及对 U937 单核细胞黏附性的影响。细胞在 TNF-α存在和不存在的情况下，用浓度从 10(-7) M 到 10(-4) M 的 SSRIs 孵育，并通过细胞 ELISA 定量 VCAM-1 和 ICAM-1 的表达。还评估了 TNF-α刺激的 U937 单核细胞黏附性。25 例慢性心力衰竭合并抑郁症患者随机分为舍曲林 50 mg，po，qd（n=13）或安慰剂。在基线和治疗 3 个月后，我们测量了 VCAM-1 和 ICAM-1 血浆水平。

结果

SSRIs 在浓度范围 10(-7) M 至 10(-4) M 时降低了 TNF-α诱导的内皮 VCAM-1 的表达（p<0.05）。在浓度为 10(-7) M 至 10(-4) M 时，氟伏沙明和氟西汀降低了 ICAM-1 的表达（p<0.05），在浓度为 10(-7) M 至 10(-5) M 时西酞普兰降低了 ICAM-1 的表达（p<0.05）。所有 SSRIs 在 10(-5) M 和 10(-4) M 时均抑制了 TNF-α刺激的 U937 细胞黏附性（p<0.05）。与基线相比，心力衰竭患者舍曲林治疗后的 ICAM-1 和 VCAM-1 水平降低幅度大于安慰剂（p<0.05）。