Journal of Thrombosis and Haemostasis最新文献

{"title":"Intravenous tenecteplase bridging reperfusion ameliorates cerebral ischemia/reperfusion injury by improving microvascular circulation in rats","authors":"Yue-Xin Ning,&nbsp;Ji-Ru Cai,&nbsp;Ting-Ting Wang,&nbsp;Yi-Han Wang,&nbsp;Yu Cui,&nbsp;Hui-Sheng Chen","doi":"10.1016/j.jtha.2024.12.042","DOIUrl":"10.1016/j.jtha.2024.12.042","url":null,"abstract":"<div><h3>Background</h3><div>Endovascular thrombectomy (EVT) alone was not demonstrated to be noninferior to intravenous alteplase bridging EVT in acute large vessel occlusion stroke. Using the cerebral ischemia/reperfusion (I/R) injury model, intravenous tenecteplase (TNK) was administrated after ischemia, followed by reperfusion at various time points.</div></div><div><h3>Objectives</h3><div>To investigate whether intravenous TNK bridging EVT vs EVT alone could improve I/R injury, and this effect may be associated with the time from TNK to reperfusion.</div></div><div><h3>Methods</h3><div>Rats received intravenous TNK (1.4 mg/kg) or vehicle (sterile water) 1.0 hours after middle cerebral artery occlusion, followed by reperfusion after 0.5 or 1.0 hours following TNK. Neurological deficit scores, infarct volume, and brain edema were measured 24 hours after middle cerebral artery occlusion. Microthrombi were determined by immunofluorescence staining for CD31⁺/fibrinogen⁺ and CD31⁺/thrombocyte⁺. Inflammatory cell infiltration in the ischemic brain region was determined by flow cytometry.</div></div><div><h3>Results</h3><div>Compared with vehicle, TNK significantly reduced neurological deficit scores, brain infarction, neuroinflammation, and blood-brain barrier disruption, and significantly reduced intravascular fibrin and platelet deposition and brain inflammatory cell infiltration in the penumbra of I/R rats. Furthermore, a better beneficial trend was found in TNK bridging reperfusion at 0.5 hours after TNK compared with TNK bridging reperfusion at 1.0 hours after TNK.</div></div><div><h3>Conclusion</h3><div>Our results demonstrate that intravenous TNK bridging reperfusion produced neuroprotective action through dissolving microvascular thrombus and alleviating inflammatory cell infiltration to improve microcirculation, with the result of maintaining blood-brain barrier integrity and inhibiting neuroinflammation, and the neuroprotective benefit may be associated with the time from TNK to reperfusion.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 4","pages":"Pages 1352-1366"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiome dysbiosis is not associated with portal vein thrombosis in patients with end-stage liver disease: a cross-sectional study","authors":"Rali R. Aleksandrova ,&nbsp;Lianne M. Nieuwenhuis ,&nbsp;Naomi Karmi ,&nbsp;Shuyan Zhang ,&nbsp;Johann Casper Swarte ,&nbsp;Johannes R. Björk ,&nbsp;Ranko Gacesa ,&nbsp;Hans Blokzijl ,&nbsp;Margery A. Connelly ,&nbsp;Rinse K. Weersma ,&nbsp;Ton Lisman ,&nbsp;Eleonora A.M. Festen ,&nbsp;Vincent E. de Meijer","doi":"10.1016/j.jtha.2024.12.036","DOIUrl":"10.1016/j.jtha.2024.12.036","url":null,"abstract":"<div><h3>Background</h3><div>Portal vein thrombosis (PVT) is a common complication in patients with end-stage liver disease (ESLD). The portal vein in patients with ESLD is proposedly an inflammatory vascular bed due to translocation of endotoxins and cytokines from the gut. We hypothesized that a proinflammatory gut microbiome and elevated trimethylamine N-oxide (TMAO), a driver of thrombosis, may contribute to PVT development.</div></div><div><h3>Objectives</h3><div>We investigated whether gut microbiome diversity, bacterial species, metabolic pathways, and TMAO levels are associated with PVT in patients with ESLD.</div></div><div><h3>Methods</h3><div>Fecal samples, plasma samples, and data from patients with ESLD and healthy controls were collected through the <em>TransplantLines</em> Biobank and Cohort Study. PVT was defined as a thrombus in the portal vein within a year prior to or after fecal sample collection. Fecal samples were analyzed using Shotgun Metagenomic Sequencing, and TMAO levels were measured in plasma using a Vantera Clinical Analyzer.</div></div><div><h3>Results</h3><div>One hundred two patients with ESLD, of which 23 with PVT, and 246 healthy controls were included. No significant difference in gut microbiome diversity was found between patients with PVT and without PVT (<em>P</em> = .18). Both ESLD groups had significantly lower alpha diversity than controls. <em>Bacteroides fragilis</em> and 3 Clostridiales species were increased in patients with PVT compared with without PVT. TMAO levels between the 3 groups were not significantly different.</div></div><div><h3>Conclusion</h3><div>We observed profound differences in gut microbiota between patients with ESLD and controls, but minimal differences between patients with ESLD with or without PVT. In our cohort, a gut-derived proinflammatory state was not associated with presence of PVT in patients with ESLD.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 4","pages":"Pages 1407-1415"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From bench to bedside: the role of tailoring fibrinolysis in pulmonary embolism","authors":"Elizabeth R. Maginot ,&nbsp;Reynold Henry ,&nbsp;Christopher D. Barrett","doi":"10.1016/j.jtha.2025.01.005","DOIUrl":"10.1016/j.jtha.2025.01.005","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 4","pages":"Pages 1205-1206"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implementation of the ISTH Framework for Professional Conduct","authors":"Ecaterina Scarlatescu ,&nbsp;Nicoletta Riva ,&nbsp;Ana I. Casanegra ,&nbsp;Cynthia Rothschild ,&nbsp;Fernanda A. Orsi ,&nbsp;Robert A.S. Ariëns ,&nbsp;ISTH Ethics Committee","doi":"10.1016/j.jtha.2025.02.040","DOIUrl":"10.1016/j.jtha.2025.02.040","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 4","pages":"Pages 1131-1132"},"PeriodicalIF":5.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refractory autoimmune heparin-induced thrombocytopenia following cardiac surgery.","authors":"Jan Zlamal, Bernhard N Bohnert, Karina Althaus, Roman Tilly, Helene Häberle, Christian Schlensak, Peter Rosenberger, Tamam Bakchoul","doi":"10.1016/j.jtha.2025.03.024","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.03.024","url":null,"abstract":"<p><p>Autoimmune heparin-induced thrombocytopenia (aHIT) is a severe subtype of HIT characterized by persistent thrombocytopenia and prothrombotic condition even though anticoagulation with heparin has been discontinued. Here we report on a patient with a previous history of aHIT where re-exposure to heparin during cardiac surgery resulted in recurrent aHIT with pulmonary embolism. Alternative anticoagulants as well as high dose intravenous immunoglobulin were ineffective, and only multiple cycles of therapeutic plasma exchange (TPE) restored platelet counts and prevented further thrombosis progression. The therapy was guided by an ex vivo model of anti-platelet factor 4 (PF4)-mediated thrombosis that showed accurate performance in predicting the clinical outcome. Most importantly, the ability to induce thrombus formation was mainly caused by anti-PF4 (heparin-independent) antibodies. Our paper provides the first description of recurrent aHIT with translational evidence that pathogenic heparin-independent anti-PF4 Abs can be specifically targeted by TPE, emphasizing the clinical use in refractory cases of aHIT.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal insights into the role of metabolites in venous thromboembolism pathogenesis: A metabolome-wide mendelian randomization study.","authors":"Wei Hu, Yun Bei, Guoquan Chen, Junjun Xu, Mingdong Yang, Lingyan Yu, Wei He, Yani Hu, Fengqian Mao, Shunan Chen, Donghang Xu, Haibin Dai","doi":"10.1016/j.jtha.2025.03.022","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.03.022","url":null,"abstract":"<p><strong>Background: </strong>Venous thromboembolism (VTE) is a significant global health burden, and metabolic alterations play a key role in its pathogenesis. However, previous studies have been constrained by several limitations, hindering clarification of the causal role of metabolites.</p><p><strong>Methods: </strong>Genetic associations involving 690 plasma and 211 urinary metabolites were analyzed as exposures, while the outcomes for VTE were derived from a large-scale meta-analysis of genome-wide association studies. Metabolome-wide Mendelian randomization (MR) and colocalization analyses were performed to assess the causal role of metabolites in VTE. Metabolic pathway analysis was performed using MetOrigin, and druggability assessments were conducted to prioritize potential therapeutic targets. Additionally, a two-step MR framework was employed to elucidate the mediating effects of metabolites on the relationships between modifiable risk factors and VTE.</p><p><strong>Results: </strong>After Bonferroni correction, 51 plasma metabolites and 18 urinary metabolites were significantly associated with VTE risk. Colocalization evidence supported causal relationships for 37 metabolites with VTE. Eleven metabolic pathways were identified for VTE-related metabolites, and six metabolites were prioritized as potential therapeutic targets. Twenty-four modifiable risk factors were associated with 28 VTE-related metabolites, seven of which were linked to VTE risk. Mediation analyses further revealed significant mediating effect of 8 metabolites on how 6 modifiable factors influenced VTE.</p><p><strong>Conclusion: </strong>This study identifies potential metabolite biomarkers associated with VTE risk and uncovered the metabolic mediators between modifiable risk factors and VTE, offering new insights for future prevention and treatment strategies.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal platelet-derived factors induce trophoblastic LAIR2 expression to promote trophoblast invasion and inhibit platelet activation at the fetal-maternal interface.","authors":"Freya Lyssy, Désirée Forstner, Jacqueline Guettler, Nadja Kupper, Kaja Ujčič, Lena Neuper, Christine Daxboeck, Amin El-Heliebi, Daniel Kummer, Julian C Krappinger, Djenana Vejzovic, Beate Rinner, Gerhard Cvirn, Stefan Wernitznig, Gerit Moser, Daniela S Valdes, Florian Herse, Anna-Lena Höbler, Juergen Pollheimer, Joanna L James, Julia Feichtinger, Martin Gauster","doi":"10.1016/j.jtha.2025.03.020","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.03.020","url":null,"abstract":"<p><strong>Background: </strong>During human placentation extravillous trophoblasts (EVTs), arising from cell column trophoblasts (CCT) invade the highly differentiated uterine mucosa, called decidua, where they erode blood vessels and replace vascular endothelial cells. Maternal platelets have been detected in intercellular gaps of CCTs but their physiological role remained unclear so far.</p><p><strong>Objective: </strong>This study aimed to elucidate the impact of platelet-derived factors on trophoblasts that are exposed to maternal platelets through erosion of decidual blood vessels.</p><p><strong>Methods: </strong>Trophoblast cell line ACH-3P spheroids were incubated either with platelet-derived factors or isolated platelets obtained from pregnant women, and afterwards subjected to RNA sequencing, and validation by qPCR, ELISA and in situ padlock hybridization. Amongst deregulated genes, LAIR2 expression was confirmed in first trimester placenta and primary trophoblast organoids. The functional role of LAIR2 in trophoblast invasion and platelet activation was studied.</p><p><strong>Results: </strong>Platelet-derived factors altered the transcription profile of ACH-3P spheroids, including deregulation of genes linked to embryonic development. Amongst them, LAIR2 was exclusively detected in CCTs and invaded EVTs of first trimester decidua. Histology showed extravasated maternal erythrocytes within interstitial gaps of highly invaded decidua samples, coinciding with LAIR2 positive EVTs. LAIR2 inhibited type 1 collagen -induced platelet activation and enhanced invasiveness of trophoblasts.</p><p><strong>Conclusion: </strong>This study suggests that maternal platelet-derived factors affect the transcription profile of trophoblasts, including upregulation of LAIR2, which may be involved in fine-tuning the coagulation of maternal blood leaking from eroded decidual blood vessels and could increase the invasiveness of EVTs into the decidua through an autocrine mechanism.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Incidence and Risk Of Venous thromboembolism in patients with Active Malignancy and Isolated Superficial Venous Thrombosis: A systematic review and meta-analysis. (The IROVAM-iSVT review).","authors":"Adrian Joseph Michel Bailey, Owen Dan Luo, Shi Qi Zhou, Phillip S Wells","doi":"10.1016/j.jtha.2025.03.019","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.03.019","url":null,"abstract":"<p><strong>Background: </strong>The management of cancer-associated isolated superficial venous thrombosis (iSVT) remains controversial as cancer patients are at higher risk of bleeding and venous thromboembolism (VTE).</p><p><strong>Objectives: </strong>We performed a systematic review and meta-analysis to determine the incidence and risk of VTE in patients with iSVT and active malignancy.</p><p><strong>Methods: </strong>Medline, Embase, Web of Science and the Cochrane Library were searched from inception to December 2nd, 2024 to identify studies investigating VTE rates in adult patients with iSVT and active malignancy. The incidence of VTE in patients with active malignancy and iSVT was pooled by meta-analysis and compared to patients with iSVT without active malignancy. Secondary outcomes included the incidence of major bleeding, clinically relevant non major bleeding (CRNMB), hospitalization, and all-cause death.</p><p><strong>Results: </strong>8 full-text studies were included comprising 5998 iSVT patients and 448 with active malignancy. Patients with cancer-associated iSVT had an overall incidence of VTE of 18.2 events per 100 patient years (95%CI [5.2-31.2], I²=76%), and a higher rate of VTE compared to patients with iSVT without active malignancy (RR 2.57, 95%CI [1.78-3.71], I²=0%, P<0.001). There were 2 major bleeding events per 100 patient years (95%CI [0 to 6.7], I²=59%) and 22.8 deaths per 100 patient years (95%CI [0 to 58.7], I² = 73%) for cancer-associated iSVT. Only one study reported on CRNMD and hospitalization rates, respectively.</p><p><strong>Conclusions: </strong>Patients with iSVT and active malignancy have high rates of VTE despite treatment. Future studies should investigate the role of extended duration anticoagulation on VTE rates in this population.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing hemostasis potency in hemophilia with a small interfering RNA targeting protein S.","authors":"Raja Prince Eladnani, Ute Schaeper, Rim Diab, Julia Aretz, Kristina Vrotniakaite-Bajerciene, Sara Çaku, Rafika Yasmin, Bojun Li, Maria Desiré Reina Caro, Sibylle Dames, Mona Eisermann, Kathrin Löffler, Alberto Martinez, Bas de Laat, Justine Brodard, Alessandro Casini, Johanna A Kremer Hovinga, Ramanjaneyulu Allam, José A Fernández, John H Griffin, Mike A Laffan, Rinku Majumder, Josefin Ahnström, Anne Angelillo-Scherrer","doi":"10.1016/j.jtha.2025.03.021","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.03.021","url":null,"abstract":"<p><strong>Background: </strong>One hemophilia treatment concept focuses on rebalancing coagulation and anticoagulation to restore normal blood clotting. Targeting the coagulation regulator, protein S (PS), in hemophilia shows promise to increase the generation of thrombin-a critical enzyme in the clotting process.</p><p><strong>Objectives: </strong>This study aimed to: (1) assess whether inhibiting PS increases thrombin generation (TG) in plasma from individuals with hemophilia A (HA) and B (HB); and (2) develop a hepatocyte-targeted PS-silencing RNA (siRNA) therapy using N-acetylgalactosamine (GalNAc) conjugation to restore hemostasis in hemophilia without increasing thromboembolic risks.</p><p><strong>Methods: </strong>We assessed TG in plasma from patients with HA and HB. To target the liver specifically, we developed a PS-siRNA conjugated with GalNAc. This approach ensures that PS levels remain adequate in other cells, thereby minimizing the risk of thrombosis. Additionally, we evaluated the therapeutic potential of PS-siRNA in preclinical models.</p><p><strong>Results: </strong>Inhibiting PS with a polyclonal antibody in plasma resulted in a 3-5 fold increase in TG in HA and a 4-9 fold increase in HB plasma, with a 70% reduction in plasma PS. In preclinical models, subcutaneous PS-siRNA therapy in HA mice and non-human primates successfully lowered PS levels and improved clot formation. It also prevented bleeding in both saphenous vein puncture and knee-injury models in HA mice. Notably, it enhanced clotting without triggering widespread clot formation.</p><p><strong>Conclusions: </strong>Reducing PS levels enhances TG in hemophilia models, and PS-siRNA therapy shows promise in improving hemostasis. This approach warrants further clinical investigation as a potential treatment for hemophilia.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasminogen and plasmin induce specialized pro-resolving mediators and promote efferocytosis via 5-lipoxygenase.","authors":"Luiza O Perucci, Fernanda S Carneiro, Josiane C Souza, Laís C Grossi, Jessica A M Souza, Isabella Zaidan, Camila Cardoso, Edvaldo S Lara, Franciel B Felix, Nagyung Baik, Luciana P Tavares, Frederico M Soriani, Mauro M Teixeira, Robert J Parmer, Lindsey A Miles, Lirlândia P Sousa","doi":"10.1016/j.jtha.2025.03.018","DOIUrl":"https://doi.org/10.1016/j.jtha.2025.03.018","url":null,"abstract":"<p><strong>Background: </strong>The plasminogen (Plg)/plasmin (Pla) system has been recognized for its pro-resolving actions, such as promoting efferocytosis. However, the role of specialized pro-resolving mediators (SPMs) in these Plg/Pla effects remains unexplored.</p><p><strong>Objectives: </strong>To investigate whether Plg/Pla promotes SPMs production in macrophages and to elucidate the role of the 5-lipoxygenase (5-LO) pathway in Pla-induced efferocytosis.</p><p><strong>Methods: </strong>Bone marrow-derived macrophages (BMDMs) from wild-type (WT) and Plg-knockout (KO) mice were treated or not with Plg/Pla, with or without leupeptin (protease inhibitor) and tranexamic acid (lysine analog), for 24 hours. SPMs and leukotriene B4 (LTB₄) production, and the mRNA expression of 5-, 12-, and 15-LO (SPMs biosynthetic enzymes) were assessed in WT-BMDMs. Additionally, 12/15-LO expression was analyzed in pleural macrophages from Pla-injected mice. Efferocytosis of apoptotic neutrophils was examined in Pla-injected WT and 5-LO KO mice and using the 5-LO inhibitor MK886 in Pla-stimulated BMDMs.</p><p><strong>Results: </strong>Plg/Pla enhanced the production of LXA₄, MaR1, and RvD1, as well as the mRNA expression of 5-, 12-, and 15-LO in macrophages, a process dependent on proteolytic activity and lysine binding sites. Macrophages from Plg KO mice produced lower LXA4 levels, while LTB₄ levels remained comparable to WT cells. Pla injection promoted macrophage recruitment to the pleural cavity alongside 12/15-LO protein upregulation. Furthermore, Pla increased the efferocytosis of apoptotic neutrophils in WT mice, but not in 5-LO KO mice, and pharmacological inhibition of 5-LO reduced Pla-induced efferocytosis in vitro.</p><p><strong>Conclusion: </strong>In summary, Plg/Pla pro-resolving actions are associated with SPMs production in macrophages and a 5-LO-dependent pro-efferocytosis mechanism.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}