Pulmonary Circulation最新文献

{"title":"Phenotypic Clustering of Idiopathic Pulmonary Arterial Hypertension: Insights Into Pulmonary Vascular and Cardiometabolic Co-Morbidity Trajectories.","authors":"Cihangir Kaymaz, Barkin Kultursay, Hacer Ceren Tokgoz, Seda Tanyeri, Cagdas Bulus, Berhan Keskin, Caglar Emre Cagliyan, Metehan Kibar, Can Erdem, Aziz Vezir, Ipek Akkus, Muhammet Bulut, Aykun Hakgor, Ibrahim Halil Tanboga, Nihal Ozdemir","doi":"10.1002/pul2.70362","DOIUrl":"10.1002/pul2.70362","url":null,"abstract":"<p><p>Idiopathic pulmonary arterial hypertension (IPAH) exhibits significant clinical heterogeneity, necessitating a precision medicine approach. This study aimed to identify distinct IPAH phenotypes using machine learning-based clustering and to evaluate their longitudinal therapeutic responses and long-term survival. We analyzed 297 IPAH patients using hierarchical agglomerative clustering based on baseline demographics, hemodynamics, and comorbidities. The cohort was characterized by two distinctive yet overlapping phenotypic patterns: Cluster 1 (<i>n</i> = 198, \"Pulmonary Vascular Phenotype\"), comprising younger patients (median age: 40) with low comorbidity burden but severe hemodynamic impairment, and Cluster 2 (<i>n</i> = 99, \"Cardiometabolic Phenotype\"), consisting of older, predominantly female patients (median age: 65) with high prevalence of obesity (78%), diabetes (73%), and hypertension (57%). Despite comparable baseline multiparametric risk scores, Cluster 1 exhibited more impaired echocardiographic right ventricular-arterial coupling, lower left ventricular filling pressure and higher pulmonary vascular resistance (<i>p</i> < 0.001). Triple combination therapy was significantly more frequent in Cluster 1 (41.6% vs. 25.5%, <i>p</i> = 0.048). Linear mixed-effects modeling over 12 months demonstrated that Cluster 1 achieved superior functional recovery (6-min walk distance increase: 75 m vs. 42 m, <i>p</i> < 0.001) and more profound neurohormonal stabilization (Final NT-proBNP: 55 vs. 145 pg/mL, <i>p</i> = 0.017). However, during a median follow-up of 763 days, 5-year survival was similar between groups (Log-rank <i>p</i> = 0.452), and cluster membership was not associated with mortality in adjusted Cox regression (HR: 0.71; 95% CI: 0.47-1.07; <i>p</i> = 0.099). These findings suggest that while vascular phenotypes demonstrate more robust responses to therapy, mortality is driven by distinct factors-hemodynamic severity in younger patients versus metabolic frailty in the comorbid population.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70362"},"PeriodicalIF":2.4,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607081","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":"Sotatercept Rescue Therapy for Acute Right Heart Failure in HIV-Associated PAH.","authors":"Yaosi Li, Daniel Grund, Nils Kremer, Holger Müller-Redetzky, Marie Zajonz, Christian Gaebler, Martin Witzenrath, Horst Olschewski, Athiththan Yogeswaran","doi":"10.1002/pul2.70379","DOIUrl":"10.1002/pul2.70379","url":null,"abstract":"<p><p>Despite major advances in antiretroviral treatment, pulmonary arterial hypertension (PAH) remains a common, severe complication in patients diagnosed with HIV. Treatment of HIV-associated PAH targets the nitric oxide, endothelin, and prostacyclin pathways, with limited evidence for novel therapies, as these patients have been excluded from most pivotal randomized controlled trials. We report a 58-year-old male with HIV-PAH on dual oral PAH-targeted therapy who developed acute right ventricular (RV) failure triggered by sepsis. Despite escalation of guideline-directed therapy with intravenous prostacyclin and catecholamines, the patient continued to exhibit decompensated right heart failure. Sotatercept was initiated, after which the patient showed marked improvement within 24 h, including improved echocardiographic RV function, a decline in NT-proBNP, recovery of renal function, and successful weaning from catecholamines and prostacyclin. The patient was subsequently transferred to a general ward in stable condition. This case suggests a potential role for sotatercept as rescue therapy in acute decompensated HIV-PAH, with a rapid temporal association with hemodynamic improvement. Further randomized controlled studies are warranted in this high-risk population.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70379"},"PeriodicalIF":2.4,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607087","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":"Long-Term Supervised Cardiac Rehabilitation After Balloon Pulmonary Angioplasty Improved Residual Exercise Pulmonary Hypertension in Patients With Chronic Thromboembolic Pulmonary Hypertension: A Two-Case Report.","authors":"Yuya Suzuki, Yoshihisa Nakano, Katsuhiro Okazaki, Momoko Ito, Anna Yoshimori, Mai Tsunoda, Masahiro Yoshida, Toko Mitsui, Shiro Adachi, Akira Kimura","doi":"10.1002/pul2.70359","DOIUrl":"10.1002/pul2.70359","url":null,"abstract":"<p><p>Abnormal pulmonary hemodynamics during exercise may persist even after balloon pulmonary angioplasty (BPA) for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). We report two female patients who underwent long-term supervised outpatient cardiac rehabilitation (CR) after BPA with continuous pulmonary vasodilators. In Case 1, training was performed at an intensity close to the anaerobic threshold. In Case 2, high-intensity interval training (HIIT) was gradually introduced. Exercise right heart catheterization was used for serial assessment of the mean pulmonary arterial pressure/cardiac output slope (mPAP/CO slope). Functional outcomes were also evaluated by cardiopulmonary exercise testing. No adverse events occurred during follow-up. The mPAP/CO slope improved from 6.28 to 4.06 mmHg/L/min at 12 months in Case 1 and from 8.40 to 6.71 mmHg/L/min at 18 months in Case 2. Peak VO₂ also increased from 16.2 to 20.2 mL/kg/min in Case 1 and from 18.3 to 24.9 mL/kg/min in Case 2. Long-term supervised outpatient CR after BPA appears to be feasible and may improve exercise pulmonary hemodynamics and exercise capacity.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70359"},"PeriodicalIF":2.4,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607015","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":"Invasive Hemodynamic Predictors of Outcomes in Rheumatic Heart Disease With Echocardiographic RV-PA Uncoupling: A Single-Center Retrospective Cohort Study.","authors":"Raissa Rafidhinar, Jordan Budiono, Melawati Hasan, Triwedya Indra Dewi, Hawani Sasmaya Prameswari, Mohammad Rizki Akbar","doi":"10.1002/pul2.70374","DOIUrl":"10.1002/pul2.70374","url":null,"abstract":"<p><p>Rheumatic heart disease (RHD) is frequently complicated by pulmonary hypertension (PH) and right ventricular (RV) dysfunction. However, the prognostic significance of invasive hemodynamic parameters obtained at index right heart catheterization (RHC) in adults with RHD and echocardiographic RV-pulmonary artery (PA) uncoupling remains incompletely defined. We evaluated their associations with all-cause mortality and a composite adverse clinical outcome. We conducted a single-center retrospective cohort study of a clinically selected group of adults with RHD and echocardiographic RV-PA uncoupling who underwent index RHC for invasive hemodynamic assessment and pre-intervention risk stratification. Parsimonious multivariable logistic regression models were used to examine adjusted associations between selected invasive hemodynamic variables and study outcomes during the available hospital-record observation period. Among 56 patients, 14 (25.0%) died during the available hospital-record observation period after the index RHC, and 23 (41.1%) experienced the composite adverse clinical outcome. In parsimonious multivariable analysis, higher pulmonary vascular resistance (PVR) remained associated with all-cause mortality after adjustment (OR 1.573, 95% CI 1.012-2.447; <i>p</i> = 0.044), whereas lower RV fractional area change (FAC) (OR 0.885, 95% CI 0.814-0.962; <i>p</i> = 0.004) and lower right ventricular stroke work index (RVSWI) (OR 0.819, 95% CI 0.670-1.000; <i>p</i> = 0.020) remained associated with the composite adverse clinical outcome. All patients met hemodynamic criteria for combined pre- and post-capillary pulmonary hypertension. In adults with RHD and echocardiographic RV-PA uncoupling who underwent clinically indicated invasive evaluation, higher PVR was associated with mortality, whereas lower FAC and lower RVSWI were associated with the composite adverse clinical outcome. These findings should be interpreted as exploratory associations derived from a clinically selected cohort and warrant confirmation in larger prospective studies.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70374"},"PeriodicalIF":2.4,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148606993","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":"A Case of High Pressure and High Stakes: Pulmonary Arterial Hypertension Emergence in an Infant With Hereditary Hemorrhagic Telangiectasia.","authors":"Amal Ahmed, Anna M Brown, Samantha J Eagle, Evan L Brittain, Anna R Hemnes, Rachel T Sullivan, Eric D Austin","doi":"10.1002/pul2.70375","DOIUrl":"10.1002/pul2.70375","url":null,"abstract":"<p><p>Hereditary hemorrhagic telangiectasia (HHT) is an autosomal‑dominant vascular disease characterized by telangiectasias and visceral arteriovenous malformations (AVMs), commonly in the lungs, liver, and brain. HHT is linked to mutations in the genes Activin A Receptor Like Type 1 (ACVRL1), Endoglin (ENG), and SMAD Family Member 4 (SMAD4). The ACVRL1 gene encodes the receptor ACVRL1 (Activin A Receptor Like Type 1), also known as ALK1 (Activin Receptor-Like Kinase 1), and belongs to the Transforming Growth Factor-Beta (TGFβ) Superfamily of receptors. Approximately 20% of patients with ACVRL1-associated HHT develop pulmonary arterial hypertension (PAH). [1] In pediatric PAH cohorts, ACVRL1 mutations account for nearly 10% of identified genetic variants. [2] The reduced penetrance of PAH among ACVRL1 mutation carriers suggests that additional modifiers account for PAH development. [3]. Given the relevance of the bone‑morphogenetic‑protein (BMP) pathway to the pathogenesis of PAH, and the intimate relationship of TGFβ superfamily signaling partners including ACVRL1 and BMPR2, genes which modify BMP-TGFβ signaling balance may contribute to PAH development in children with ACVRL1‑positive HHT. One such gene is SMAD9 (Receptor Regulated SMAD 9); the protein product of SMAD 9 (SMAD8) which mediates downstream TGFβ signaling. Herein, we report what we believe to be the youngest reported case of PAH in ACVRL1‑mediated HHT, in a patient who co‑harbors a SMAD9 mutation.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70375"},"PeriodicalIF":2.4,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148606892","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":"Functional Role of Piezo1 in Regulating Whole-Lung Vascular Reactivity.","authors":"Sophia Parmisano, Jiyuan Chen, Yuqin Chen, Pritesh P Jain, Lauren Yung, Wei-Ting Wang, Ting Wang, Xiang Li, Angela Balistrieri, Sophia A Ferrizzi, Cassia Pedron, Owen Brooks, Mona Alotaibi, Jian Wang, Joe G N Garcia, Patricia A Thistlethwaite, Ayako Makino, Jason X-J Yuan","doi":"10.1002/pul2.70371","DOIUrl":"10.1002/pul2.70371","url":null,"abstract":"<p><p>Mechanosensitive cation channels expressed in pulmonary arterial smooth muscle (SMC) and endothelial (EC) cells contribute to the regulation of vasoconstriction and vasodilation of the pulmonary vasculature. Here, we report that activating Piezo1, a mechanosensitive cation channel, with Yoda1 induced a mild increase in pulmonary arterial pressure (PAP) via vasoconstriction in the intact pulmonary vascular system. Inhibition of nitric oxide (NO) synthase (NOS) with l-NAME significantly potentiated Yoda1-mediated pulmonary vasoconstriction. The Yoda1-mediated vasoconstriction was inhibited by Gd³⁺, a non-selective blocker of cation channels, but not affected by nifedipine, a dihydropyridine blocker of voltage-dependent Ca²⁺ channels (VDCC). Alveolar hypoxia alone increased PAP via hypoxic pulmonary vasoconstriction (HPV); Yoda1-mediated pulmonary vasoconstriction overlaps with HPV in the isolated and perfused/ventilated lung. On top of the Yoda1-mediated increase in PAP, intrapulmonary perfusion of high K⁺ (25 mM) solution or phenylephrine (PE, 30 µM) induced an additional increase in PAP. These data indicate that, under normal conditions, the activation of Piezo1 (by Yoda1) caused pulmonary vasodilation due to Ca²⁺-associated activation of NOS in ECs and vasoconstriction due to Ca²⁺ influx in SMCs. In conclusion, Piezo1 or Ca²⁺ influx through Piezo1 in ECs and SMCs functions differently in the regulation of pulmonary vasculature. When the endothelium-derived relaxing factor (e.g., NO) is decreased due to EC injury and/or inflammation, Piezo1 or Ca²⁺ influx through Piezo1 channels is an important trigger for pulmonary vasoconstriction in the whole-lung vascular system.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70371"},"PeriodicalIF":2.4,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148606943","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":"Poncirin Alleviates Hypoxic Pulmonary Hypertension by Blocking TDP43-Mediated Macrophage Pyroptosis.","authors":"Jiao Yue, Peng Wang, Hao Liu, Haifeng Pei","doi":"10.1002/pul2.70368","DOIUrl":"10.1002/pul2.70368","url":null,"abstract":"<p><p>This study aimed to investigate the therapeutic effects of Poncirin on hypoxic pulmonary hypertension (HPH) and to elucidate the underlying mechanism, with a specific focus on transactive response DNA-binding protein 43 (TDP43)-mediated macrophage pyroptosis. A rat model of HPH was established using a hypobaric hypoxia chamber. In vitro, rat alveolar macrophages (NR8383 cells) and pulmonary artery smooth muscle cells (PASMCs) were cultured under normoxic or hypoxic (1% O₂) conditions. TDP43 expression was modulated through small interfering RNA (siRNA)-mediated knockdown or lentivirus-mediated overexpression. Poncirin was administered at a dose of 30 mg/kg in vivo and at a concentration of 50 μM in vitro to assess its pharmacologic effects. The results demonstrated that TDP43 expression was markedly upregulated in lung tissues of rats with HPH and in hypoxia-exposed NR8383 cells, and this was accompanied by increased macrophage accumulation around pulmonary arterioles. Hypoxia-induced TDP43 upregulation promoted macrophage pyroptosis via activation of NLRP3, Caspase 1, and N-GSDMD, leading to enhanced release of the inflammatory cytokine interleukin-1β (IL-1β), which in turn facilitated PASMCs proliferation. Poncirin significantly attenuated hypoxia-induced macrophage pyroptosis and PASMCs proliferation in both in vivo and in vitro models by downregulating TDP43 expression. Collectively, these findings identify TDP43 as a key mediator in the pathogenesis of HPH and support Poncirin as a potential therapeutic agent for HPH through targeting of TDP43-mediated macrophage pyroptosis.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70368"},"PeriodicalIF":2.4,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607096","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":"Poverty and Social Deprivation in Patients With Pulmonary Arterial Hypertension-A PHAR Analysis.","authors":"Roberto J Bernardo, Di Lu, Haley Hedlin, Daniel Grinnan, Roberto F Machado, Lana Melendres-Groves, Jean M Elwing, Sandeep Sahay, Steven M Kawut, Jeffrey C Robinson, Vinicio A de Jesus Perez, Roham T Zamanian","doi":"10.1002/pul2.70373","DOIUrl":"10.1002/pul2.70373","url":null,"abstract":"<p><p>Poverty and social deprivation have been associated with impaired clinical outcomes and survival in several chronic diseases. The association between poverty and clinical outcomes in patients with pulmonary arterial hypertension (PAH) remains unclear. We aim to determine the association between federal poverty levels with healthcare use and clinical outcomes in PAH. Using the Pulmonary Hypertension Association Registry, we performed a prospective cohort analysis comparing clinical and socioeconomic characteristics in PAH patients above or below federal poverty levels. We studied the association between federal poverty levels and healthcare use patterns and transplant-free survival using a Cox proportional hazards model. A total of 1396 participants were included, 411 (29.4%) under poverty levels. The in-poverty group was mostly non-White and Hispanic, had mainly public health insurance/Medicaid (37.0% vs. 5.5%; absolute standardized difference [ASD] 0.84), lower educational attainment (17.2% vs. 45.6% college graduate or higher; ASD 0.64), lower rates of employment/retirement (27.3% vs. 71.1%; ASD 0.98), higher frequency of methamphetamine exposure (31.5% vs. 9.8%; ASD 0.57), and lower frequency of idiopathic/heritable PAH (36.0% vs. 47.8%; ASD 0.65), than the not in-poverty group. While there were no differences in severity of disease or treatment, the in-poverty group had higher incidence rate ratios of emergency room visits and hospitalizations (IRR 2.19, 95% CI 1.99-2.40, and 1.51, 95% CI 1.36-1.68, respectively). There were no differences in transplant-free survival (<i>p</i> = 0.10). Poverty was not associated with worse survival in patients with PAH but was associated with higher rates of emergency room visits and hospitalizations, suggesting suboptimal disease control despite similar disease severity.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70373"},"PeriodicalIF":2.4,"publicationDate":"2026-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607106","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":"Effectiveness of PAH Specific Treatment Is Comparable Between PAH Associated With Connective Tissue Disease and Idiopathic PAH: Data From the Multicentre National Registry.","authors":"Anna Smukowska-Gorynia, Sylwia Iwańczyk, Michał Ciurzyński, Marcin Waligóra, Marcin Kurzyna, Piotr Pruszczyk, Grzegorz Kopeć, Katarzyna Mizia-Stec, Ilona Skoczylas, Łukasz Chrzanowski, Piotr Błaszczak, Katarzyna Ptaszyńska, Grzegorz Grześk, Ewa Malinowska, Małgorzata Peregud-Pogorzelska, Michał Tomaszewski, Ewa Mroczek, Miłosz Jaguszewski, Ewa Lewicka, Katarzyna Widejko, Agnieszka Pawlak, Wojciech Jacheć, Zbigniew Gąsior, Katarzyna Betkier-Lipińska, Judyta Winowska-Józwa, Marta Banaszkiewicz, Tatiana Mularek-Kubzdela","doi":"10.1002/pul2.70370","DOIUrl":"10.1002/pul2.70370","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is a rare disease with poor prognosis. The same treatment is recommended in patients with PAH associated with connective tissue disease (CTD) and idiopathic PAH (IPAH). However, the effectiveness of PAH-specific treatment in these both groups is inconsistent. The study incorporated data from the prospective, multicentre polish registry (BNP-PL) by comparison of baseline versus 1-year follow-up clinical, laboratory, echocardiographic and hemodynamic parameters in PAH-CTD versus IPAH group. The all-cause 1-year mortality was also analysed. 624 patients were included in the study: 176 (28%) PAH-CTD and 448 (72%) IPAH. 48 (8% of the total 624) patients died during 1-year follow up: 32 (7%) with IPAH and 16 (9%) with PAH-CTD (<i>p</i> = 0.4). The effectiveness of treatment was examined in 421 patients: 115 (27%) PAH-CTD and 306 (73%) IPAH. The improvement of treatment was effective in both groups in terms of WHO FC (<i>p</i> < 0.001 in both groups), 4-strata risk model (<i>p</i> < 0.001 in both groups), 6 min walking test (6MWT, <i>p</i> < 0.001 in IPAH, <i>p</i> = 0.001 in PAH-CTD), Δ6MWT (<i>p</i> = 0.19 between PAH-CTD and IPAH), tricuspid annular plane systolic excursion (<i>p</i> < 0.001 in both groups), NT- proBNP (<i>p</i> < 0.001 in IPAH and <i>p</i> < 0.01 in PAH-CTD), mean pulmonary arterial pressure (<i>p</i> = 0.043 in IPAH and <i>p</i> = 0.01 in PAH-CTD), pulmonary vascular resistance (<i>p</i> < 0.001 in both groups) and cardiac output (<i>p</i> < 0.001 in IPAH and <i>p</i> = 0.034 in PAH-CTD). PAH specific treatment in PAH-CTD patients is as effective as in IPAH patients regarding improvement in WHO FC, 4-strata risk model, 6MWT, Δ6MWT, TAPSE, NT-proBNP, mPAP, PVR and CO at 1-year follow-up. 1-year all-cause mortality was not significantly different between PAH-CTD and IPAH patients.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70370"},"PeriodicalIF":2.4,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148607004","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":"Evidence for PDZ-Binding Kinase in Lung Disease With an Emphasis on PAH.","authors":"Scott A Barman, Zsuzsanna Bordan, David J R Fulton","doi":"10.1002/pul2.70369","DOIUrl":"10.1002/pul2.70369","url":null,"abstract":"<p><p>Originally named T-cell-originated Lymphokine-activated killer protein kinase (TOPK), PDZ-Binding Kinase (PBK) is a serine/threonine kinase that is a member of the family of mitogen-activated protein kinases (MAPKKs), which is overexpressed in lung cancer and interstitial pulmonary fibrosis (IPF). Along these lines, recent work also shows that PBK expression is upregulated in pulmonary arterial hypertension (PAH) in part due to the inappropriate proliferation of pulmonary arterial smooth muscle cells (PASMC), similar to the hyper-proliferative cellular properties seen in both lung cancer and IPF. Genetic knock-out of PBK as well as pharmacologically selective inhibitors of PBK improve PA remodeling and cardiopulmonary function. Further, PBK bound to the Protein Regulator of Cytokinesis 1 (PRC1) induces PRC1 phosphorylation and cytokinesis in PASMC, and thus, it is conjectured that PBK enhances PASMC proliferation via PRC1-mediated cytokinesis, identifying a key mechanism which contributes to the pathologic pulmonary vascular remodeling that occurs in PAH. Towards this end, along with the already published studies showing that PBK is involved in both lung cancer and IPF, PBK-mediated pulmonary vascular remodeling reveals a new signaling pathway in lung vascular disease and a novel mechanism of PASMC proliferation. Exploration of this signaling pathway will advance the utility of identifying novel therapeutic approaches targeting PBK-mediated cytokinesis to reduce pulmonary vascular remodeling (as seen in PAH) and subsequently improve the morbidity and mortality associated with lung vascular disease. Collectively, the literature strongly suggests that PBK is a worthy and viable therapeutic target to pursue in the context of lung disease.</p>","PeriodicalId":20927,"journal":{"name":"Pulmonary Circulation","volume":"16 3","pages":"e70369"},"PeriodicalIF":2.4,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148606980","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}