2nd Department of Cardiology, Attikon Hospital, University of Athens, School of Medicine, Athens, Greece.
Int J Cardiol. 2010 Mar 4;139(2):150-8. doi: 10.1016/j.ijcard.2008.10.010. Epub 2008 Nov 11.
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.
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.
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).
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.
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。
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。
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）。
SSRIs 可能对内皮细胞具有抗炎活性，并降低体内循环中的 VCAM-1 和 ICAM-1，这一机制可能部分介导其心脏保护作用。
