Splenectomy is modifying the vascular remodeling of thrombosis.
Splenectomy is modifying the vascular remodeling of thrombosis.
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DOI：
10.1161/jaha.113.000772
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发表时间：
2014-02-28
影响因子：
5.4
通讯作者：
Lang IM
中科院分区：
文献类型：
--
作者：
Frey MK;Alias S;Winter MP;Redwan B;Stübiger G;Panzenboeck A;Alimohammadi A;Bonderman D;Jakowitsch J;Bergmeister H;Bochkov V;Preissner KT;Lang IM
脾切除术是复杂血栓形成的临床危险因素。我们推测脾脏机械过滤功能的丧失可能导致循环中血栓形成的磷脂富集，从而影响血栓的血管重塑。我们研究了脾切除术对慢性血栓栓塞性肺动脉高压（CTEPH）（一种血栓未消退的人类模型疾病）和模拟深静脉血栓形成的滞流静脉血栓形成的小鼠模型的影响。从曾接受过脾切除术的罕见 CTEPH 患者中通过手术切除的血栓富含阴离子磷脂，如磷脂酰丝氨酸。与人类血栓类似，小鼠模型脾切除后，磷脂酰丝氨酸在血栓中积聚。脾切除术后状态与更大且更持久的血栓相关。脾切除后，小鼠体内促凝血小板微粒数量增加，白细胞-血小板聚集体增加。组织学检查显示血栓血管数量减少。富含磷脂酰丝氨酸的磷脂特异性抑制内皮细胞增殖和发芽。脾切除术后，实验性血栓诱导增强了循环微粒和带负电磷脂的增加。脾切除后血栓体积最初增加是由于血小板活化，随后血栓消退的延迟是由于血栓血管生成的抑制。这些数据说明了 CTEPH 疾病的潜在机制。
Splenectomy is a clinical risk factor for complicated thrombosis. We hypothesized that the loss of the mechanical filtering function of the spleen may enrich for thrombogenic phospholipids in the circulation, thereby affecting the vascular remodeling of thrombosis. We investigated the effects of splenectomy both in chronic thromboembolic pulmonary hypertension (CTEPH), a human model disease for thrombus nonresolution, and in a mouse model of stagnant flow venous thrombosis mimicking deep vein thrombosis. Surgically excised thrombi from rare cases of CTEPH patients who had undergone previous splenectomy were enriched for anionic phospholipids like phosphatidylserine. Similar to human thrombi, phosphatidylserine accumulated in thrombi after splenectomy in the mouse model. A postsplenectomy state was associated with larger and more persistent thrombi. Higher counts of procoagulant platelet microparticles and increased leukocyte–platelet aggregates were observed in mice after splenectomy. Histological inspection revealed a decreased number of thrombus vessels. Phosphatidylserine‐enriched phospholipids specifically inhibited endothelial proliferation and sprouting. After splenectomy, an increase in circulating microparticles and negatively charged phospholipids is enhanced by experimental thrombus induction. The initial increase in thrombus volume after splenectomy is due to platelet activation, and the subsequent delay of thrombus resolution is due to inhibition of thrombus angiogenesis. The data illustrate a potential mechanism of disease in CTEPH.