TGF-β-Induced Autophagy in Pulmonary Artery Endothelial Cells Associated with Chronic  Thromboembolic Pulmonary Hypertension

TGF-β-Induced Autophagy in Pulmonary Artery Endothelial Cells Associated with Chronic Thromboembolic Pulmonary Hypertension | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article TGF-β-Induced Autophagy in Pulmonary Artery Endothelial Cells Associated with Chronic Thromboembolic Pulmonary Hypertension Ying-Ju Lai, Yen-Lin Huang, Ching-Yen Tsai, Po-Ru Chen, Chi-Jen Chang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7316454/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Mar, 2026 Read the published version in Journal of Molecular Medicine → Version 1 posted 5 You are reading this latest preprint version Abstract Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive vascular disorder characterized by persistent thromboembolic obstruction and fibrotic remodeling of the pulmonary arteries. Although autophagy has been implicated in various forms of pulmonary hypertension, its specific role in CTEPH pathogenesis remains unclear. In this study, histological, immunohistochemical, and molecular analyses of pulmonary artery lesions from CTEPH patients revealed increased collagen deposition and elevated expression of autophagy markers beclin-1 and microtubule-associated protein 1A/1B-light chain 3 (LC3) compared to non-CTEPH controls. Primary pulmonary artery endothelial cells (PAECs) derived from CTEPH patients exhibited dysregulated autophagy-related protein expression. Mechanistically, TGF-β stimulation induced autophagy via the Smad3 signaling pathway. Notably, riociguat, a soluble guanylate cyclase stimulator approved for CTEPH, modulated autophagy-related proteins in vitro. In hypoxia- and TGF-β-induced pulmonary hypertension mouse models, riociguat attenuated LC3 but not beclin-1 expression and significantly reduced right ventricular systolic pressure. These findings suggest that LC3 may be a key autophagy marker in CTEPH. These findings identify the TGF-β/Smad3-LC3 axis as a critical mechanism driving CTEPH and suggest that pharmacological modulation of autophagy, particularly via riociguat, offers a promising therapeutic opportunity, especially for patients ineligible for surgical intervention. Autophagy LC3 riociguat CTEPH Full Text Supplementary Files KeyMessages.pdf autophagyinCTEPHuncutblotting.pdf Cite Share Download PDF Status: Published Journal Publication published 30 Mar, 2026 Read the published version in Journal of Molecular Medicine → Version 1 posted Editorial decision: Major Revisions Needed 10 Oct, 2025 Reviewers agreed at journal 31 Aug, 2025 Reviewers invited by journal 29 Aug, 2025 Editor assigned by journal 19 Aug, 2025 First submitted to journal 14 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7316454","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":507348212,"identity":"c1c2cad4-52c3-4512-a12d-51c7613bb4fa","order_by":0,"name":"Ying-Ju 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