ADAMTS13 inhibits H2O2-induced human venous endothelial cell injury to attenuate deep-vein thrombosis by blocking the p38/ERK signaling pathway.

Deep vein thrombosis (DVT) is a common complication in hematologic malignancies and immunologic disorders. Endothelial cell injury and dysfunction comprise the critical contributor for the development of DVT. A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13), a plasma metalloprotease that cleaves von Willebrand factor, acts as a critical regulator in normal hemostasis. This study was aimed to explore the role of ADAMTS13 in endothelial cell injury during DVT and the possible mechanism. First, human umbilical vein endothelial cells (HUVECs) were exposed to hydrogen peroxide (H2O2). Then, the mRNA and protein expressions of ADAMTS13 were evaluated with the reverse transcription-quantitative polymerase chain reaction and western blot. After treatment with recombinant ADAMTS13 (rADAMTS13; rA13), the viability and apoptosis of H2O2-induced HUVECs were assessed by cell counting kit-8 assay and terminal-deoxynucleoitidyl transferase-mediated nick end labeling staining. In addition, the levels of prostaglandin F1-alpha, endothelin-1, and reactive oxygen species were detected using the enzyme-linked immunosorbent assay and dichloro-dihydro-fluorescein diacetate assay. The expressions of proteins related to p38/extracellular signal-regulated kinase (ERK) signaling pathway were estimated with the western blot. Then, p79350 (p38 agonist) was used to pretreat cells to analyze the regulatory effects of rA13 on p38/ERK signaling in H2O2-induced HUVEC injury. The results revealed that ADAMTS13 expression was significantly downregulated in H2O2-induced HUVECs. The reduced viability and increased apoptosis of HUVECs induced by H2O2 were revived by ADAMTS13. ADAMTS13 also suppressed the oxidative stress in HUVECs after H2O2 treatment. Besides, ADAMTS13 was found to block p38/ERK signaling pathway, and p79350 reversed the impacts of ADAMTS13 on the damage of HUVECs induced by H2O2. To sum up, ADAMTS13 could alleviate H2O2-induced HUVEC injury through the inhibition of p38/ERK signaling pathway.

AngioJet thrombectomy in the treatment of pulmonary embolism complicated with left subclavian artery embolism: a case report.

Coexistence of pulmonary embolism (PE) and arterial thrombosis in a single patient is rare. Management of such cases is challenging because there is no unified standard on how to treat this type of disease. We herein report a case involving a 73-year-old man who was admitted to the hospital because of a 2-day history of chest tightness. Pulmonary computed tomography angiography revealed a filling defect of the main pulmonary artery and bilateral branches as well as a left subclavian artery embolism. AngioJet mechanical thrombectomy (Boston Scientific, Marlborough, MA, USA) was used to treat the PE, and this was combined with left brachial artery incision and thrombectomy for treatment of the left subclavian artery embolism. The patient recovered well after the operation. The prognosis was good after 9 months of regular follow-up. AngioJet mechanical thrombectomy combined with left brachial artery incision thrombectomy may be a feasible treatment option for cases of PE combined with left subclavian artery embolism.