Pulmonary Circulation最新文献

{"title":"Non-invasive surrogates for right Ventricular-Pulmonary arterial coupling: a systematic review and Meta-Analysis.","authors":"Jem M Golbin, Neehal Shukla, Neil Nero, Maxwell A Hockstein, Adriano R Tonelli, Matthew T Siuba","doi":"10.1002/pul2.70004","DOIUrl":"https://doi.org/10.1002/pul2.70004","url":null,"abstract":"<p><p>Right ventricle-pulmonary artery (RV-PA) coupling describes the energetic relationship between RV contractility and its afterload. The gold standard for assessment of this relationship requires invasive pressure-volume (PV) loop measurements. Non-invasive surrogates of RV-PA coupling have been developed, such as the echocardiographic tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio (TAPSE/PASP), but their performance has not been systematically assessed. We sought to assess performance of TAPSE/PASP ratio compared to PV loop-defined RV-PA coupling. A systematic search was conducted. Studies were included if PV loop derived RV-PA coupling metrics were compared to echocardiographic or magnetic resonance imaging surrogates. We conducted a meta-analysis of TAPSE/PASP correlation to PV loop-defined RV-PA coupling. 1452 studies were identified in the initial search, of which ten met inclusion criteria. Five studies allowed for pooled analysis of TAPSE/PASP to Ees/Ea correlation (<i>r</i> = 0.52, 95% confidence interval 0.36-0.65). There was moderate heterogeneity across the pooled studies. Despite the common use of Non-invasive surrogates of RV-PA coupling, there is only moderate correlation with gold standard measurements. These metrics do not inform on the individual components of RV-PA coupling, limiting their use in the management of patients with RV dysfunction.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e70004"},"PeriodicalIF":2.2,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Congruency between clinician-assessed risk and calculated risk of 1-year mortality in patients with pulmonary arterial hypertension: A retrospective chart review.","authors":"Amresh Raina, Margaret R Sketch, Benjamin Wu, Meredith Broderick, Oksana A Shlobin","doi":"10.1002/pul2.12455","DOIUrl":"10.1002/pul2.12455","url":null,"abstract":"<p><p>The objective of this analysis was to compare clinician-based and formally calculated risk assessments by REVEAL Lite 2 and COMPERA 2.0 and to characterize parenteral prostacyclin utilization within 90 days of baseline in high-risk patients. A multisite, double-blind, retrospective chart review of patients with pulmonary arterial hypertension (PAH) was conducted with an index period of January 2014-March 2017. Patients were categorized into the \"any PAH medication\" or \"prostacyclin-enriched\" cohort based on latest PAH medication initiated within the index period. Clinicians classified the patient's 1-year mortality risk as \"low,\" \"intermediate,\" or \"high\" based on their clinical assessment. REVEAL Lite 2 and COMPERA 2.0 scores were independently calculated. Risk assessment congruency was evaluated. Parenteral prostacyclin use was evaluated within 90 days of baseline. Thirty-two clinicians participated and abstracted data for 299 patients with PAH. At baseline, mean patient age was 52 years, 6-min walk distance was 226 m, and most patients were WHO functional class II or III. Half of the patients (53%) were classified by clinician assessment as intermediate risk, while most were classified as high risk by REVEAL Lite 2 (59%) and intermediate-high risk by COMPERA 2.0 (52%). Parenteral prostascyclins were underutilized in high-risk patients, and not initiated in a timely fashion. Clinician-assessed risk category was incongruent with tool-based risk assessments in 40%-54% of patients with PAH, suggesting an underestimation of the patient's risk category by clinician gestalt. Additionally, there was a lack of timely prostacyclin initiation for patients with PAH stratified as high-risk by either tool.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e12455"},"PeriodicalIF":2.2,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Barriers to and facilitators of physical activity in pediatric pulmonary hypertension.","authors":"Catherine M Avitabile, Caroline O'Brien, Divya Dureja, Dana Albizem, Jena Mota, Melissa Xanthopoulos, Babette S Zemel, Peter F Cronholm","doi":"10.1002/pul2.70000","DOIUrl":"https://doi.org/10.1002/pul2.70000","url":null,"abstract":"<p><p>Therapeutic exercise has not been widely adopted in pediatric pulmonary hypertension (PH), despite adult data supporting its safety and efficacy. While physical limitations may prevent children with PH from participating in physical activity, other barriers to and facilitators of physical activity are unknown. Youth ages 8-18 years with World Symposium of PH diagnostic Groups 1-4, functional class I or II, and ambulatory status were prospectively enrolled in a cross-sectional study including separate 30-min participant and caregiver interviews regarding attitudes toward physical activity and a proposed exercise intervention in pediatric PH. Interview questions were guided by Social Cognitive Theory and explored autonomy, self-confidence, and self-efficacy. Interviews were transcribed, coded, and analyzed using an iterative process to determine themes and patterns. Demographics and relevant PH condition-specific data were abstracted from the medical record. Thirty PH participant/caregiver dyads were interviewed. Facilitators of physical activity included enjoyment/interest in the activity, socialization, incentivization, and feelings of safety and normalcy. Barriers to physical activity included lack of interest, fear/anxiety, and self-consciousness. Findings were similar in children and adults. Participants rarely reported restriction of activity by caregivers or medical providers. Attitudes toward engagement in a proposed exercise program were generally positive and reflected personal experiences with physical activity. Monitored exercise interventions that focus on patients' interests, cultivate confidence, respect limitations, and acknowledge the need for extrinsic incentivization may have benefits in pediatric PH. Future trials should test the impact of these characteristics on patient wellbeing and clinical outcomes.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e70000"},"PeriodicalIF":2.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostacyclin pathway vasodilators in patients with chronic thromboembolic pulmonary hypertension (CTEPH): A systemic review and meta-analysis of randomized controlled trials.","authors":"Weijun Li, Xingxue Pang, Jun Chen, Xiaoxia Ren, Huaibing Zhao, Xu Wang, Ning Zhao, Dayi Hu, Zhongyi Jin","doi":"10.1002/pul2.70001","DOIUrl":"https://doi.org/10.1002/pul2.70001","url":null,"abstract":"<p><p>Although surgical and interventional therapy has emerged as the primary treatment for patients with chronic thromboembolic pulmonary hypertension (CTEPH), there remains a subset of patients who need medication therapy. This study aimed to evaluate the efficacy and safety outcomes of prostacyclin pathway vasodilators, providing further insight for clinical decision-making. A literature search was conducted in PubMed, Embase, and CENTRAL databases from inception to December 2023. Literature screening and quality assessment were carried out with the Cochrane Risk of Bias Tool. Data analysis was conducted using RevMan 5.4 software. We included 6 randomized controlled trials with 387 patients. Prostacyclin pathway vasodilators demonstrated a significant improvement in PVR (-125.26 dynes·sec·cm^-5, 95%CI: -219.29 to -31.23, <i>Z</i> = 2.61, and <i>p</i> < 0.009), RAP (-0.78 mmHg, 95%CI: -1.52 to -0.04, <i>Z</i> = 2.06, and <i>p</i> = 0.04), cardiac index (0.62, 95%CI: 0.54 to 0.69, <i>Z</i> = 16.13, and <i>p</i> < 0.00001), and the number of patients showing improvement in WHO functional class (3.86, 95%CI: 1,92 to 7.77, <i>Z</i> = 3.79, and <i>p</i> = 0.0002) compared to controls, moreover, a trend towards improvement was observed in mPAP, 6MWD, and NT-proBNP. Regarding the safety endpoints, no significant difference was found in both groups in terms of serious adverse events and all-cause deaths. The prostacyclin pathway vasodilators present therapeutic potential for CTEPH patients with inoperable or persistent/recurrent PH after PEA/BPA primarily characterized by distal small-vessel and microvasculopathy. However, the current clinical evidence remains insufficient and controversial, necessitating further validation.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e70001"},"PeriodicalIF":2.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The influence of the NRG1/ERBB4 signaling pathway on pulmonary artery endothelial cells.","authors":"Jin-Bo Huang, Qin Shen, Zhi-Qi Wang, Song-Shi Ni, Fei Sun, Yun Hua, Jian-An Huang","doi":"10.1002/pul2.12439","DOIUrl":"https://doi.org/10.1002/pul2.12439","url":null,"abstract":"<p><p>This study aimed to examine the influence of the Neuregulin-1 (NRG1)/ERBB4 signaling pathway on the function of human pulmonary artery endothelial cells (HPAECs) and investigate the underlying mechanisms. Enzyme-linked immunosorbent assay indicated that ERBB4 levels in the serum of patients with pulmonary embolism (PE) were significantly higher than those of healthy controls (<i>p</i> < 0.05). In cellular studies, thrombin stimulation for 6 h led to a significant decrease in cell viability and overexpression of ERBB4 compared to control (<i>p</i> < 0.05). In the NRG1 group, apoptosis of HPAECs was reduced (<i>p</i> < 0.05), accompanied by a decrease in ERBB4 expression and an increase in p-ERBB4, phosphorylated serine/threonine kinase proteins (Akt) (p-Akt), and p-phosphoinositide 3-kinase (PI3K) expression (<i>p</i> < 0.05). In the AG1478 group, there was a significant increase in HPAEC apoptosis and a significant decrease in p-ERBB4 and ERBB4 expression compared to the Con group (<i>p</i> < 0.05). In the AG1478 + NRG1 group, there was an increase in the apoptosis rate and a significant decrease in the expression of p-ERBB4, ERBB4, p-Akt, and phosphorylated PI3K compared to the NRG1 group (<i>p</i> < 0.05). In animal studies, the PE group showed an increase in the expression of ERBB4 and p-ERBB4 compared to the Con group (<i>p</i> < 0.05). NRG1 treatment led to a significant reduction in embolism severity with decreased ERBB4 expression and increased p-ERBB4 expression (<i>p</i> < 0.05). Gene set enrichment analysis identified five pathways that were significantly associated with high ERBB4 expression, including CHOLESTEROL HOMEOSTASIS, OXIDATIVE PHOSPHORYLATION, and FATTY ACID METABOLISM (<i>p</i> < 0.05). Therefore, NRG1 inhibits apoptosis of HPAECs, accompanied by a decrease in ERBB4 and an increase in p-ERBB4. NRG1 inhibition in HPAECs apoptosis can be partially reversed by inhibiting ERBB4 expression with AG1478. ERBB4 has the potential to be a novel biological marker of PE.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e12439"},"PeriodicalIF":2.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ventricular interdependent phenotype of mixed Cpc-pulmonary hypertension and HFpEF with normal left atrium: Impact on CPET metrics and clinical outcomes.","authors":"Giovanna Zampierollo-Jaramillo, Anas Abed, Ahmed El Shaer, Mariana Garcia-Arango, Yimin Chen, Babak Tehrani, Wanxin Tu, Abdul Wahab Arif, Shannon Heffernan, Amir Esmaeeli, Aditya Sahai, James Runo, Aurangzeb Baber, Sofia C Masri, Farhan Raza","doi":"10.1002/pul2.12449","DOIUrl":"https://doi.org/10.1002/pul2.12449","url":null,"abstract":"<p><p>Among 45 CpcPH/heart failure with preserved ejection fraction participants, 11 with normal left atrium (compared to 34 with abnormal left atrium, <i>p</i> < 0.05 for all) had low left ventricle (LV) transmural pressure (2.9 ± 2.4 vs. 6.2 ± 2.9 mmHg), and increased right ventricle (RV):LV ratio (2.41 ± 1.09 vs. 1.46 ± 0.66) and interventricular septal angle (149 ± 8 vs. 136 ± 10), indicating exaggerated ventricular interdependence from a dilated RV.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e12449"},"PeriodicalIF":2.2,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practices affEcting macitentan and selexipag patient persistence Rates utilizing pulmonary arterial hypertension clinical Site and patIent perSpecTives (PERSIST): a US qualitative analysis.","authors":"Oksana A Shlobin, Gary Bruce, Gabriela Gomez-Rendon, Martha Kingman, Mohammad Rahman, Frances Rogers, Sean Studer, Tobore Tobore, Colleen McEvoy","doi":"10.1002/pul2.12441","DOIUrl":"https://doi.org/10.1002/pul2.12441","url":null,"abstract":"<p><p>This real-world study explored factors affecting persistence with macitentan and selexipag treatment from the perspective of 23 healthcare professionals (HCPs) and 134 patients with pulmonary arterial hypertension between 2019 and 2022. Continuous patient/HCP communication and education were key drivers of persistence, as were early discussion and management of side effects.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e12441"},"PeriodicalIF":2.2,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiopulmonary exercise testing following acute pulmonary embolism: Systematic review and pooled analysis of global studies.","authors":"Gabriella VanAken, Daniel Wieczorek, Drew Rubick, Ahmad Jabri, Domingo Franco-Palacios, Gillian Grafton, Bryan Kelly, Olusegun Osinbowale, Syed T Ahsan, Rana Awdish, Herbert D Aronow, Supriya Shore, Vikas Aggarwal","doi":"10.1002/pul2.12451","DOIUrl":"10.1002/pul2.12451","url":null,"abstract":"<p><p>Recent reports have revealed a substantial morbidity burden associated with \"post-PE syndrome\" (PPES). Cardiopulmonary exercise testing (CPET) has shown promise in better characterizing these patients. In this systematic review and pooled analysis, we aim to use CPET data from PE survivors to understand PPES better. A literature search was conducted in PubMed, EMBASE, and Cochrane for studies reporting CPET results in post-PE patients without known pulmonary hypertension published before August 1, 2023. Studies were independently reviewed by two authors. CPET findings were subcategorized into (1) exercise capacity (percent predicted pVO₂ and pVO₂) and (2) ventilatory efficiency (VE/VCO₂ slope and V_D/V_T). We identified 14 studies (<i>n</i> = 804), 9 prospective observational studies, 4 prospective case-control studies, and 1 randomized trial. Pooled analysis demonstrated a weighted mean percent predicted pVO₂ of 76.09 ± 20.21% (<i>n</i> = 184), with no difference between patients tested <6 months (<i>n</i> = 76, 81.69±26.06%) compared to ≥6 months post-acute PE (<i>n</i> = 88, 82.55 ± 21.47%; <i>p</i> = 0.817). No difference was seen in pVO₂ in those tested <6 months (<i>n</i> = 76, 1.67 ± 0.51 L/min) compared to ≥6 months post-acute PE occurrence (<i>n</i> = 144, 1.75 ± 0.57 L/min; <i>p</i> = 0.306). The weighted mean VE/VCO₂ slope was 32.72 ± 6.02 (<i>n</i> = 244), with a significant difference noted between those tested <6 months (<i>n</i> = 91, 36.52 ± 6.64) compared to ≥6 months post-acute PE (<i>n</i> = 191, 31.99 ± 5.7; <i>p</i> < 0.001). In conclusion, this study, which was limited by small sample sizes and few multicenter studies, found no significant difference in exercise capacity between individuals tested <6 months versus ≥6 months after acute PE. However, ventilatory efficiency was significantly improved in patients undergoing CPET ≥ 6 months compared to those <6 months from the index PE.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e12451"},"PeriodicalIF":2.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PPARγ/ETV2 axis regulates endothelial-to-mesenchymal transition in pulmonary hypertension.","authors":"Dong Hun Lee, Minseong Kim, Sarah S Chang, Raham Lee, Andrew J Jang, Juyoung Kim, Jing Ma, Michael J Passineau, Raymond L Benza, Harry Karmouty-Quintana, Wilbur A Lam, Benjamin T Kopp, Roy L Sutliff, C Michael Hart, Changwon Park, Bum-Yong Kang","doi":"10.1002/pul2.12448","DOIUrl":"10.1002/pul2.12448","url":null,"abstract":"<p><p>Endothelial-to-mesenchymal transition (EndoMT) plays an important role in pulmonary hypertension (PH) but the molecular mechanisms regulating EndoMT remain to be defined. We demonstrate that the axis of the transcription factors PPARγ (Peroxisome Proliferator-Activated Receptor gamma) and ETV2 (ETS variant 2) play important roles in the pathogenesis of PH. Decreased levels of the expression of PPARγ and ETV2 along with reduced endothelial and increased EndoMT markers are consistently observed in lungs and pulmonary artery endothelial cells (PAECs) of idiopathic pulmonary arterial hypertension patients, in hypoxia-exposed mouse lungs, human PAECs, and in induced-EndoMT cells. <i>Etv2</i> ^<i>+/-</i> mice spontaneously developed PH and right ventricular hypertrophy (RVH), associated with increased EndoMT markers and decreased EC markers. Interestingly, chronic hypoxia exacerbated right ventricular systolic pressure and RVH in <i>Etv2</i> ^<i>+/-</i> mice. PPARγ transcriptionally activates the ETV2 promoter. Consistently, while mice overexpressing endothelial PPARγ increases the expression of ETV2 and endothelial markers with reduced EndoMT markers, endothelial PPARγ KO mice show decreased ETV2 expression and enhanced EndoMT markers. Inducible overexpression of <i>ETV2</i> under induced-EndoMT cell model reduces number of cells with mesenchymal morphology and decreases expression of mesenchymal markers with increased EC makers, compared to control. Therefore, our study suggests that PPARγ-ETV2 signaling regulates PH pathogenesis through EndoMT.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e12448"},"PeriodicalIF":2.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Didang decoction attenuates cancer-associated thrombosis by inhibiting PAD4-dependent NET formation in lung cancer.","authors":"Xiaoyan Zeng, Jiuxi Li, Liyuan Pei, Yaping Yang, Ya Chen, Xuejing Wang, Ting Zhang, Ting Zhou","doi":"10.1002/pul2.12454","DOIUrl":"10.1002/pul2.12454","url":null,"abstract":"<p><p>This research aims to investigate the impact of Didang decoction (DD) on the formation of neutrophil extracellular traps (NETs) and cancer-associated thrombosis in lung cancer. BALB/c nude mice were used to establish xenograft models for inducing deep vein thrombosis. Tumor growth and thrombus length were assessed. The impact of DD on NET generation was analyzed using enzyme-linked immunosorbent assay, immunofluorescence staining, quantitative real-time PCR, and western blot analysis, both in vivo and in vitro. CI-amidine, a PAD4 inhibitor, was employed to evaluate the role of PAD4 in the generation of NETs. In vivo studies demonstrated that treatment with DD reduced tumor growth, inhibited thrombus formation, and decreased the levels of NET markers in the serum, tumor tissues, neutrophils, and thrombus tissues of mice. Additional data indicated that DD could suppress neutrophil counts, the release of tissue factor (TF), and the activation of thrombin-activated platelets, all of which contributed to increased formation of NETs in mouse models. In vitro, following incubation with conditioned medium (CM) derived from Lewis lung carcinoma cells, the expression of NET markers in neutrophils was significantly elevated, and an extracellular fibrous network structure was observed. Nevertheless, these NET-associated changes were partially counteracted by DD. Additionally, CI-amidine reduced the expression of NET markers in CM-treated neutrophils, consistent with the effects of DD. Collectively, DD inhibits cancer-associated thrombosis in lung cancer by decreasing PAD4-dependent NET formation through the regulation of TF-mediated thrombin-platelet activation. This presents a promising therapeutic strategy for preventing and treating venous thromboembolism in lung cancer.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"14 4","pages":"e12454"},"PeriodicalIF":2.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}