Bender Matthew T, Aggarwal Anu, Godwin Matthew, Guntupalli Suman, Nanjundappa Aravinda, Tefera Leben, Haddadin Ihab, Tong Michael, Baldwin William M, Fairchild Robert L, Gomes Marcelo, Campbell Joseph, Schumick David, Chaudhury Pulkit, Mix Doran, Cameron Scott J
Department of Neurological Surgery, University of Rochester, Rochester, NY.
Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland, OH.
Blood Vessel Thromb Hemost. 2024 Sep 23;2(1):100029. doi: 10.1016/j.bvth.2024.100029. eCollection 2025 Feb.
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; = .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.
血栓形成后血管重塑的机制尚不清楚。尽管脑血管循环中的急性动脉血栓会产生毁灭性后果且需要立即关注，但静脉血栓栓塞（VTE）的治疗方法却有很大差异。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成分，以深入了解血管重塑。25例患者接受了导管定向血栓切除术（CDT）；13例因脑血管意外（CVA），8例因肺栓塞，4例因深静脉血栓形成。从血栓中提取蛋白质和RNA，以进行免疫印迹、RNA测序和基因表达定量分析。CVA患者从症状出现到血栓提取的时间为7.7±1.9小时，VTE患者为109±55小时。静脉血栓中的蛋白质浓度、白细胞含量（单核细胞）和红细胞含量均高于动脉血栓，而血小板含量相似。静脉和动脉血栓均含有几种属于基质金属蛋白酶（MMP）家族的锌内肽酶。静脉血栓中的MMP9活性高于动脉血栓（每微克蛋白质61±9纳克/毫升 vs 每微克蛋白质25±6纳克/毫升；P = 0.005）。动脉和静脉血栓表现出惊人的不同表型，具有促进血管重塑的生物活性酶，且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在静脉循环中避免不可逆血管重塑的作用。
