Mutations in the gene for the transforming growth factor (TGF)-beta superfamily receptor, bone morphogenetic protein receptor II, underlie heritable forms of pulmonary arterial hypertension (PAH). Aberrant signaling via TGF-beta receptor I/activin receptor-like kinase 5 may be important for both the development and progression of PAH. We investigated the therapeutic potential of a well-characterized and potent activin receptor-like kinase 5 inhibitor, SB525334 [6-(2-tert-butyl-5-{6-methyl-pyridin-2-yl}-1H-imidazol-4-yl)-quinoxaline] for the treatment of PAH. In this study, we demonstrate that pulmonary artery smooth muscle cells from patients with familial forms of idiopathic PAH exhibit heightened sensitivity to TGF-beta1 in vitro, which can be attenuated after the administration of SB525334. We further demonstrate that SB525334 significantly reverses pulmonary arterial pressure and inhibits right ventricular hypertrophy in a rat model of PAH. Immunohistochemical studies confirmed a significant reduction in pulmonary arteriole muscularization induced by monocrotaline (used experimentally to induce PAH) after treatment of rats with SB525334. Collectively, these data are consistent with a role for the activin receptor-like kinase 5 in the progression of idiopathic PAH and imply that strategies to inhibit activin receptor-like kinase 5 signaling may have therapeutic benefit.
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http://dx.doi.org/10.2353/ajpath.2009.080565 | DOI Listing |
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Department of Cardiology, West China Hospital, Sichuan University West China School of Medicine, 37 Guoxue Road, Chengdu, Sichuan, 610041, China.
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January 2025
Department of Neonatology, Children's Hospital of Soochow University, Suzhou, China.
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Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Imaging, National Taiwan University Cancer Center, Taipei, Taiwan.
Background And Purpose: Dual-energy computed tomography (DECT) pulmonary angiography can reliably detect cement pulmonary embolisms (CPEs) and parenchymal perfusion defects. This prospective observational study investigated CPEs in asymptomatic patients using DECT.
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Department of Medicine, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8558, USA; Department of Pediatrics, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8558, USA. Electronic address:
Pulmonary vascular diseases, particularly when accompanied by pulmonary hypertension, are complex disorders often requiring multimodal imaging for diagnosis and monitoring. Echocardiography is the primary screening tool for pulmonary hypertension, while cardiac MR imaging (CMR) is used for more detailed characterization and risk stratification in right ventricular failure. Chest computed tomography (CT) is used to detect vascular anomalies and parenchymal lung diseases.
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Section of Interventional Radiology, Department of Radiology, University of Washington, Box 357233, 1959 Northeast Pacific Street, Seattle, WA 98195, USA.
Endovascular intervention is a safe, effective treatment modality in the management of diverse pulmonary vascular pathologies, including acute or chronic thromboembolic disease, pulmonary arteriovenous malformations (pAVMs), pulmonary artery or bronchial artery hemorrhage, and foreign body retrieval. This article reviews indications, contraindications, techniques, and outcomes in endovascular management of common pulmonary vascular pathologies, with the goal of improving operator familiarity and facility with these procedures.
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