RETINOIC ACID REDUCES INDUCTION OF MONOCYTE TISSUE FACTOR AND TISSUE FACTOR FACTOR VIIA-DEPENDENT ARTERIAL THROMBUS FORMATION
RETINOIC ACID REDUCES INDUCTION OF MONOCYTE TISSUE FACTOR AND TISSUE FACTOR FACTOR VIIA-DEPENDENT ARTERIAL THROMBUS FORMATION
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DOI：
10.1182/blood.v86.1.212.bloodjournal861212
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发表时间：
1995-07-01
期刊：
影响因子：
20.3
通讯作者：
SAKARIASSEN, KS
中科院分区：
文献类型：
--
作者：
BARSTAD, RM;HAMERS, MJAG;SAKARIASSEN, KS
下调单核细胞/巨噬细胞组织因子（TF）活性诱导的药物可能会降低与血管通畅性机械恢复或人工动脉移植相关的血栓形成风险。在这种情况下，动脉粥样硬化斑块中的促凝血巨噬细胞和粘附于人造材料的促凝血单核细胞可能暴露于血流。石井等人（Blood 80：2556，1992）报道了内皮TF的诱导被全反式视黄酸（ATRA）下调，Conese等人（Thromb Haemost 66：662，1991）报道了类视黄酸下调单核细胞促凝血活性（PCA）。这些发现使我们研究ATRA对单核细胞TF表达的影响，并在人动脉血栓形成模型系统中研究ATRA对单核细胞诱导的血栓形成的影响。ATRA剂量依赖性地降低0.5 μ g/mL脂多糖（LPS）诱导的人外周血单核细胞PCA，在10（-5）mol/L ATRA时降低56%（P <0.0001）。ATRA浓度为10（-6）mol/L时，LPS诱导的TF抗原表达降低38%（P <0.0007）。单核细胞与塑料盖片（Thermanox，Miles Labs，纳珀维尔，伊利诺伊州）的粘附也引发了细胞PCA的诱导，抗TF单克隆抗体（MoAb）可抑制80%以上（P < .002）。加入ATRA（10（-6）mol/L）可使PCA减少40%（P <0.03），TF抗原表达减少30%（P <0.0001）。将Thermanox粘附的单核细胞暴露于平行板灌注室装置中的Rowing非抗凝人血中，动脉壁剪切速率为650 s（-1），引起显著的纤维蛋白沉积和血小板血栓形成。10（-6）mol/LATRA可部分阻断血栓形成，使纤维蛋白沉积减少80%（P <0.02），血小板血栓形成减少50%（P <0.05）。相比之下，在血液暴露之前将粘附的单核细胞与抗TF MoAb孵育，使纤维蛋白沉积减少83%（P < .02），血小板血栓体积减少75%（P < .0008）。因此，ATRA是单核细胞TF-PCA的有效下调剂，并且可以减少斑块破裂部位、经皮腔内血管成形术后斑块破裂处或人工动脉移植引入的表面上的血栓形成并发症。(C)1995年，美国血液学会。
Agents that downregulate the induction of monocyte/macrophage tissue factor (TF) activity may attenuate the thrombotic risk associated with mechanical restoration of vessel patency or artificial arterial grafting. In such events, procoagulant macrophages in the atherosclerotic plaque and procoagulant monocytes adherent to artificial materials may be exposed to the blood stream. Ishii et al (Blood 80:2556, 1992) reported that induction of endothelial TF is downregulated by all-trans retinoic acid (ATRA), and Conese et al (Thromb Haemost 66:662, 1991) reported that retinoids downregulate monocyte procoagulant activity (PCA). These findings led us to investigate the effect of ATRA on monocyte TF expression, and to study the effect of ATRA on monocyte-induced thrombus formation in a model system of human arterial thrombogenesis. Induction of PCA in human peripheral blood monocytes by 0.5 mu g/mL lipopolysaccharide (LPS) was dose dependently reduced by ATRA, reaching a reduction of 56% at 10(-5) mol/L ATRA (P < .0001). A 38% reduction (P < .0007) in LPS-induced TF antigen expression was observed at an ATRA concentration of 10(-6) mol/L. Adherence of monocytes to plastic cover slips (Thermanox, Miles Laboratories, Naperville, IL) also triggered induction of cellular PCA, which was inhibited by more than 80% by an anti-TF monoclonal antibody (MoAb) (P < .002). Inclusion of ATRA (10(-6) mol/L) reduced this PCA by 40% (P < .03), and the TF antigen expression by 30% (P < .0001). Exposure of Thermanox adherent monocytes to Rowing nonanticoagulated human blood in a parallel-plate perfusion chamber device at an arterial wall shear rate of 650 s(-1) elicited significant fibrin deposition and platelet thrombus formation. Partial interruption of this thrombus formation was achieved by 10(-6) mol/L ATRA, which reduced the fibrin deposition by 80% (P < .02) and platelet thrombus formation by 50% (P < .05). In comparison, incubation of adherent monocytes with the anti-TF MoAb before the blood exposure, reduced the fibrin deposition by 83% (P < .02) and platelet thrombus volume by 75% (P < .0008). Thus, ATRA is an effective down-regulator of monocyte TF-PCA, and may reduce thrombotic complications at sites of plaque rupture, at plaque disruption after percutaneous transluminal angioplasty procedures, or on surfaces introduced by artificial arterial grafting. (C) 1995 by The American Society of Hematology.