The role of platelets in thrombus fibrosis and vessel wall remodeling after venous thrombosis.
The role of platelets in thrombus fibrosis and vessel wall remodeling after venous thrombosis.
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DOI：
10.1111/jth.15134
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Wagner DD
中科院分区：
文献类型：
--
作者：
DeRoo E;Martinod K;Cherpokova D;Fuchs T;Cifuni S;Chu L;Staudinger C;Wagner DD
已知血小板在静脉血栓形成中起重要作用，但它们在血栓成熟、溶解和血栓形成后静脉壁重塑中的作用尚不清楚。本研究的目的是确定循环中的血小板在静脉血栓形成的后期中所起的作用。我们采用小鼠下腔静脉(IVC)狭窄模型。在未经治疗的小鼠中进行基线研究，以确定血栓后组织采集的最佳时间点，该时间点将捕捉血栓成熟/溶解和血栓后静脉壁重构。于术后第2天行下腔静脉超声检查确定静脉血栓形成后，每日注射血小板耗竭抗体(抗GP1bα)维持血小板减少状态，同时给予对照组，直至术后第10天，取下腔静脉和血栓，分析血栓长度、体积、纤维化程度、新生血管形成和平滑肌细胞侵袭情况。同时检测静脉壁纤维化和血管内膜增厚。静脉血栓形成后导致血小板减少的小鼠血栓纤维化程度较低，侵袭的平滑肌细胞较少。此外，静脉血栓形成时的血小板减少导致血栓后静脉壁内膜增厚较少。血栓体积在血小板减少的小鼠和对照小鼠之间没有差异。本研究提示，循环中的血小板参与了静脉血栓的成熟、纤维化和不良的静脉壁重构，抑制血小板募集可能减少血栓和静脉壁纤维化，从而有助于血栓的溶解和预防血栓后综合征。
Platelets are known to play an important role in venous thrombogenesis, but their role in thrombus maturation, resolution, and postthrombotic vein wall remodeling is unclear. The purpose of this study was to determine the role that circulating platelets play in the later phases of venous thrombosis. We used a murine inferior vena cava (IVC) stenosis model. Baseline studies in untreated mice were performed to determine an optimal postthrombotic time point for tissue harvest that would capture both thrombus maturation/resolution and postthrombotic vein wall remodeling. This time point was found to be postoperative day 10. After undergoing IVC ultrasound on day 2 to confirm venous thrombus formation, mice were treated with a daily injection of platelet-depleting antibody (anti-GP1bα) to maintain thrombocytopenia or with control IgG until postoperative day 10, at which time IVC and thrombi were harvested and thrombus length, volume, fibrosis, neovascularization, and smooth muscle cell invasion analyzed. Vein wall fibrosis and intimal thickening were also determined. Mice that were made thrombocytopenic after venous thrombogenesis had thrombi that were less fibrotic, with fewer invading smooth muscle cells. Furthermore, thrombocytopenia in the setting of venous thrombosis resulted in less postthrombotic vein wall intimal thickening. Thrombus volume did not differ between thrombocytopenic mice and their control peers. This work suggests that circulating platelets contribute to venous thrombus maturation, fibrosis, and adverse vein wall remodeling, and that that inhibition of platelet recruitment may decrease thrombus and vein wall fibrosis, thus helping thrombolysis and preventing postthrombotic syndrome.
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影响因子：
10.8
作者：
Brill, A;Elinav, H;Varon, D
通讯作者：
Varon, D
DOI：
10.1073/pnas.0510412103
发表时间：
2006-01-24
影响因子：
11.1
作者：
Kisucka, J;Butterfield, CE;Wagner, DD
通讯作者：
Wagner, DD
影响因子：
37.8
作者：
Benjamin, Emelia J.;Virani, Salim S.;Muntner, Paul
通讯作者：
Muntner, Paul
影响因子：
7.3
作者：
Chrysanthopoulou, Akrivi;Mitroulis, Ioannis;Kambas, Konstantinos
通讯作者：
Kambas, Konstantinos
影响因子：
4.3
作者：
Deatrick, KB;Eliason, JL;Henke, PK
通讯作者：
Henke, PK