{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:47:51Z","timestamp":1790887671844,"version":"4.1.0"},"reference-count":80,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Merck Investigators Studies Program","award":["MISP 101592"],"award-info":[{"award-number":["MISP 101592"]}]},{"name":"Cleveland Clinic Innovative Respiratory Institute Chairman\u2019s Award","award":["IF110346"],"award-info":[{"award-number":["IF110346"]}]},{"name":"Cleveland Clinic Research Program Committee grant","award":["3169"],"award-info":[{"award-number":["3169"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pulmonary arterial pressures that can lead to right heart failure and death. No cure exists for this disease, but therapeutic advancements have extended its median survival from 2 to 7 years. Mechanistic research in PAH has been limited by factors including that a) animal models do not fully recapitulate the disease or provide insights into its pathogenesis, and b) cellular material from PAH patients is primarily obtained from donor lungs during autopsy or transplantation, which reflect end-stage disease. Therefore, there is a need to identify tools that can elucidate the specific mechanisms of human disease in individual patients, a critical step to guide treatment decisions based on specific pathway abnormalities. Here we demonstrate a simple method to isolate and culture circulating endothelial cells (CECs) obtained at the time of right heart catheterization in PAH patients. We tested these CECs using transcriptomics and found that they have typical traits of PAH, including those involving key treatment pathways, i.e. nitric oxide, endothelin, prostacyclin and BMP\/activin pathways. CECs show important gene expression changes in other central PAH disease pathways. In summary, we present a new cellular model for the ex-vivo mechanistic evaluation of critical PAH pathways that participate in the pathogenesis of the disease and may help personalized therapeutic decisions.<\/jats:p>","DOI":"10.1371\/journal.pone.0312535","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T17:40:17Z","timestamp":1730137217000},"page":"e0312535","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characteristic disease defects in circulating endothelial cells isolated from patients with pulmonary arterial hypertension"],"prefix":"10.1371","volume":"19","author":[{"given":"Kulwant S.","family":"Aulak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori","family":"Mavarakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3666-7424","authenticated-orcid":true,"given":"Deborah","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzy A.","family":"Comhair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raed A.","family":"Dweik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2321-9545","authenticated-orcid":true,"given":"Adriano R.","family":"Tonelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"issue":"3","key":"pone.0312535.ref001","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1164\/rccm.201209-1640OC","article-title":"Causes and circumstances of death in pulmonary arterial hypertension","volume":"188","author":"AR Tonelli","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"pone.0312535.ref002","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.00879-2022","article-title":"2022 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension","volume":"61","author":"M Humbert","year":"2023","journal-title":"Eur Respir J"},{"issue":"4","key":"pone.0312535.ref003","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1378\/chest.15-0300","article-title":"Five-Year outcomes of patients enrolled in the REVEAL Registry","volume":"148","author":"HW Farber","year":"2015","journal-title":"Chest"},{"issue":"123","key":"pone.0312535.ref004","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1183\/09059180.00008211","article-title":"REVEAL: a contemporary US pulmonary arterial hypertension registry","volume":"21","author":"MD McGoon","year":"2012","journal-title":"Eur Respir Rev"},{"issue":"1","key":"pone.0312535.ref005","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.jacc.2009.04.006","article-title":"Inflammation, growth factors, and pulmonary vascular remodeling","volume":"54","author":"PM Hassoun","year":"2009","journal-title":"J Am Coll Cardiol"},{"issue":"1","key":"pone.0312535.ref006","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.01887-2018","article-title":"Pathology and pathobiology of pulmonary hypertension: state of the art and research perspectives","volume":"53","author":"M Humbert","year":"2019","journal-title":"Eur Respir J"},{"issue":"1","key":"pone.0312535.ref007","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ccl.2021.08.001","article-title":"The Pathobiology of Pulmonary Arterial Hypertension","volume":"40","author":"S Rajagopal","year":"2022","journal-title":"Cardiol Clin"},{"issue":"2","key":"pone.0312535.ref008","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1378\/chest.11-1460","article-title":"An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry","volume":"142","author":"RL Benza","year":"2012","journal-title":"Chest"},{"key":"pone.0312535.ref009","article-title":"FDA approves Merck & Co\u2019s pulmonary arterial hypertension drug sotatercept","author":"K. 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