Cellular and enzymatic features of thrombi in humans are vascular bed dependent

Blood Vessels, Thrombosis & Hemostasis Pub Date : 2025-02-01 DOI:10.1016/j.bvth.2024.100029

Matthew T. Bender ∗ , Anu Aggarwal ∗ , Matthew Godwin , Suman Guntupalli , Aravinda Nanjundappa , Leben Tefera , Ihab Haddadin , Michael Tong , William M. Baldwin III , Robert L. Fairchild , Marcelo Gomes , Joseph Campbell , David Schumick , Pulkit Chaudhury , Doran Mix , Scott J. Cameron

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Abstract

Mechanisms behind vascular remodeling following thrombosis are unclear. Although acute arterial thrombosis in the cerebrovascular circulation has devastating consequences and requires immediate attention, the management of venous thromboembolism (VTE) varies significantly. Our goal was to determine the molecular signatures and cellular content of thrombus extracted using a catheter to gain insight into vascular remodeling. Twenty-five patients underwent catheter-directed thrombectomy (CDT); 13 for cerebrovascular accident (CVA), 8 for pulmonary embolism, and 4 for deep vein thrombosis. Protein and RNA were extracted from thrombi to enable immunoblotting, RNA sequencing, and quantification of gene expression. The time from symptom onset to thrombus extraction was 7.7 ± 1.9 hours for CVA and 109 ± 55 hours for VTE. Protein concentration, white blood cell content (monocytes), and red blood cell content were greater in venous thrombus than in arterial thrombus, whereas the platelet content was similar. Both venous and arterial thrombi contained several zinc endopeptidases belonging to the matrix metalloproteinase (MMP) family. MMP9 activity in venous thrombus was greater than arterial thrombus (61 ± 9 ng/mL per μg protein vs 25 ± 6 ng/mL per μg protein; P = .005). Arterial and venous thrombi displayed surprisingly different phenotypes, with biologically active enzymes promoting blood vessel remodeling and enzymatic activity proportional to thrombus age extracted from the veins. These mechanistic data may support the role of early CDT in venous circulation to avoid irreversible vascular remodeling.

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人类血栓的细胞和酶的特征是依赖于血管床的

血栓形成后血管重构的机制尚不清楚。尽管脑血管循环中的急性动脉血栓形成具有破坏性后果，需要立即关注，但静脉血栓栓塞（VTE）的治疗方法差异很大。我们的目标是确定使用导管提取的血栓的分子特征和细胞含量，以深入了解血管重塑。25例患者行导管定向取栓术（CDT）；脑血管意外（CVA） 13例，肺栓塞8例，深静脉血栓形成4例。从血栓中提取蛋白质和RNA，进行免疫印迹、RNA测序和基因表达定量。CVA从症状出现到取出血栓的时间为7.7±1.9小时，VTE为109±55小时。静脉血栓的蛋白质浓度、白细胞含量（单核细胞）和红细胞含量高于动脉血栓，而血小板含量相似。静脉血栓和动脉血栓均含有多种锌内肽酶，属于基质金属蛋白酶（MMP）家族。静脉血栓中的MMP9活性高于动脉血栓（61±9 ng/mL / μg蛋白vs 25±6 ng/mL / μg蛋白）；p = .005)。动脉血栓和静脉血栓表现出令人惊讶的不同表型，生物活性酶促进血管重塑，酶活性与从静脉中提取的血栓年龄成正比。这些机制数据可能支持早期CDT在静脉循环中的作用，以避免不可逆的血管重塑。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Blood Vessels, Thrombosis & Hemostasis

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