{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T17:27:16Z","timestamp":1773422836149,"version":"3.50.1"},"reference-count":22,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:00:00Z","timestamp":1608249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"This work was partially supported by the European Regional Development Fund (ERDF) and `Fondo de Investigaci\u00f3n Sanitaria\u00b4 [PI18\/00043] from Instituto de Salud Carlos III (ISCIII), Health Ministry, Spain.","award":["PI18\/00043"],"award-info":[{"award-number":["PI18\/00043"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Interstitial lung disease (ILD) increases morbidity and mortality in patients with rheumatoid arthritis (RA). Although the pathogenesis of ILD associated with RA (RA-ILD+) remains poorly defined, vascular tissue is crucial in lung physiology. In this context, endothelial progenitor cells (EPC) are involved in endothelial tissue repair. However, little is known about their implication in RA-ILD+. Accordingly, we aimed to investigate the potential role of EPC related to endothelial damage in RA-ILD+. EPC quantification in peripheral blood from 80 individuals (20 RA-ILD+ patients, 25 RA-ILD\u2212 patients, 21 idiopathic pulmonary fibrosis (IPF) patients, and 14 healthy controls) was performed by flow cytometry. EPC were considered as CD34+, CD45low, CD309+ and CD133+. A significant increase in EPC frequency in RA-ILD+ patients, as well as in RA-ILD\u2212 and IPF patients, was found when compared with controls (p &lt; 0.001, p = 0.02 and p &lt; 0.001, respectively). RA-ILD+ patients exhibited a higher EPC frequency than the RA-ILD\u2212 ones (p = 0.003), but lower than IPF patients (p &lt; 0.001). Our results suggest that EPC increase may represent a reparative compensatory mechanism in patients with RA-ILD+. The degree of EPC frequency may help to identify the presence of ILD in RA patients and to discriminate RA-ILD+ from IPF.<\/jats:p>","DOI":"10.3390\/jcm9124098","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T04:12:01Z","timestamp":1608523921000},"page":"4098","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Endothelial Progenitor Cells as a Potential Biomarker in Interstitial Lung Disease Associated with Rheumatoid Arthritis"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3534-8467","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"Pulito-Cueto","sequence":"first","affiliation":[{"name":"Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Santander, 39011 Cantabria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4455-7241","authenticated-orcid":false,"given":"Sara","family":"Remuzgo-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Santander, 39011 Cantabria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3612-1448","authenticated-orcid":false,"given":"Fernanda","family":"Genre","sequence":"additional","affiliation":[{"name":"Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Santander, 39011 Cantabria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8161-0462","authenticated-orcid":false,"given":"V\u00edctor M.","family":"Mora-Cuesta","sequence":"additional","affiliation":[{"name":"Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Santander, 39011 Cantabria, Spain"},{"name":"Department of Pneumology, Hospital Universitario Marqu\u00e9s de Valdecilla, Santander, 39008 Cantabria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5241-266X","authenticated-orcid":false,"given":"David","family":"Iturbe-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Santander, 39011 Cantabria, Spain"},{"name":"Department of Pneumology, Hospital Universitario Marqu\u00e9s de Valdecilla, Santander, 39008 Cantabria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Fern\u00e1ndez-Rozas","sequence":"additional","affiliation":[{"name":"Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Santander, 39011 Cantabria, Spain"},{"name":"Department of Pneumology, Hospital Universitario Marqu\u00e9s de Valdecilla, Santander, 39008 Cantabria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7119-0786","authenticated-orcid":false,"given":"Bel\u00e9n","family":"Atienza-Mateo","sequence":"additional","affiliation":[{"name":"Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Santander, 39011 Cantabria, Spain"},{"name":"L\u00f3pez Albo\u2019 Post-Residency Programme, Hospital Universitario Marqu\u00e9s de Valdecilla, Santander, 39008 Cantabria, Spain"},{"name":"Department of Rheumatology, Hospital Universitario Marqu\u00e9s de Valdecilla, Santander, 39008 Cantabria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leticia","family":"Lera-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Santander, 39011 Cantabria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pilar","family":"Alonso-Lecue","sequence":"additional","affiliation":[{"name":"Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Santander, 39011 Cantabria, Spain"},{"name":"Department of Pneumology, Hospital Universitario Marqu\u00e9s de Valdecilla, Santander, 39008 Cantabria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Rodr\u00edguez-Carrio","sequence":"additional","affiliation":[{"name":"Department of Functional Biology, Immunology Area, Faculty of Medicine, Universidad de Oviedo, Oviedo, 33006 Asturias, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Prieto-Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Santander, 39011 Cantabria, Spain"},{"name":"Department of Rheumatology, Hospital Universitario Marqu\u00e9s de Valdecilla, Santander, 39008 Cantabria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia","family":"Portilla","sequence":"additional","affiliation":[{"name":"Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Santander, 39011 Cantabria, Spain"},{"name":"Department of Rheumatology, Hospital Universitario Marqu\u00e9s de Valdecilla, Santander, 39008 Cantabria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2344-2285","authenticated-orcid":false,"given":"Ricardo","family":"Blanco","sequence":"additional","affiliation":[{"name":"Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Santander, 39011 Cantabria, Spain"},{"name":"Department of Rheumatology, Hospital Universitario Marqu\u00e9s de Valdecilla, Santander, 39008 Cantabria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfonso","family":"Corrales","sequence":"additional","affiliation":[{"name":"Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Santander, 39011 Cantabria, Spain"},{"name":"Department of Rheumatology, Hospital Universitario Marqu\u00e9s de Valdecilla, Santander, 39008 Cantabria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7154-1328","authenticated-orcid":false,"given":"Oreste","family":"Gualillo","sequence":"additional","affiliation":[{"name":"SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigaci\u00f3n Sanitaria de Santiago), NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, Santiago University Clinical Hospital, Santiago de Compostela, 15706 A Coru\u00f1a, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 M.","family":"Cifri\u00e1n","sequence":"additional","affiliation":[{"name":"Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Santander, 39011 Cantabria, Spain"},{"name":"Department of Pneumology, Hospital Universitario Marqu\u00e9s de Valdecilla, Santander, 39008 Cantabria, Spain"},{"name":"School of Medicine, Universidad de Cantabria, Santander, 39005 Cantabria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"L\u00f3pez-Mej\u00edas","sequence":"additional","affiliation":[{"name":"Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Santander, 39011 Cantabria, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7924-7406","authenticated-orcid":false,"given":"Miguel A.","family":"Gonz\u00e1lez-Gay","sequence":"additional","affiliation":[{"name":"Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Santander, 39011 Cantabria, Spain"},{"name":"Department of Rheumatology, Hospital Universitario Marqu\u00e9s de Valdecilla, Santander, 39008 Cantabria, Spain"},{"name":"School of Medicine, Universidad de Cantabria, Santander, 39005 Cantabria, Spain"},{"name":"Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2050, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bendstrup, E., Moller, J., Kronborg-white, S., Prior, T.S., and Hyldgaard, C. (2019). Interstitial Lung Disease in Rheumatoid Arthritis Remains a Challenge for Clinicians. J. Clin. Med., 8.","DOI":"10.3390\/jcm8122038"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"h6819","DOI":"10.1136\/bmj.h6819","article-title":"Management of interstitial lung disease associated with connective tissue disease","volume":"352","author":"Mathai","year":"2016","journal-title":"BMJ"},{"key":"ref_3","first-page":"280","article-title":"Rheumatoid Arthritis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis: Shared Mechanistic and Phenotypic Traits Suggest Overlapping Disease Mechanisms","volume":"67","author":"Paulin","year":"2015","journal-title":"Rev. Investig. Cl\u00edn."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Atienza-Mateo, B., Remuzgo-Mart\u00ednez, S., Mora-Cuesta, V.M., Iturbe-Fern\u00e1ndez, D., Fern\u00e1ndez-Rozas, S., Prieto-Pe\u00f1a, D., Calder\u00f3n-Goercke, M., Corrales, A., Blanco-Rodriguez, G., and G\u00f3mez-Rom\u00e1n, J.J. (2020). The Spectrum of Interstitial Lung Disease Associated with Autoimmune Diseases: Data of a 3.6-Year Prospective Study from a Referral Center of Interstitial Lung Disease and Lung Transplantation. J. Clin. Med., 9.","DOI":"10.3390\/jcm9061606"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1152\/ajplung.00314.2007","article-title":"Lung microvascular endothelium is enriched with progenitor cells that exhibit vasculogenic capacity","volume":"294","author":"Alvarez","year":"2008","journal-title":"Lung. Cell Mol. Physiol."},{"key":"ref_6","first-page":"964","article-title":"Isolation of Putative Progenitor Endothelial Cells for Angiogenesis","volume":"275","author":"Asahara","year":"1997","journal-title":"Sci. New Ser."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"R27","DOI":"10.1186\/ar2934","article-title":"Enhanced late-outgrowth circulating endothelial progenitor cell levels in rheumatoid arthritis and correlation with disease activity","volume":"12","author":"Avouac","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1093\/rheumatology\/kes152","article-title":"Circulating endothelial cells and their progenitors in systemic lupus erythematosus and early rheumatoid arthritis patients","volume":"51","author":"Prado","year":"2012","journal-title":"Rheumatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1002\/art.24921","article-title":"Endothelial Progenitor Cells Novel Players in the Pathogenesis of Rheumatic Diseases","volume":"60","author":"Distler","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jbspin.2007.09.006","article-title":"Endothelial progenitor cells and rheumatic disorders","volume":"75","author":"Avouac","year":"2008","journal-title":"Jt. Bone Spine"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"De Biasi, S., Cerri, S., Bianchini, E., Gibellini, L., Persiani, E., Montanari, G., Luppi, F., Carbonelli, C.M., Zucchi, L., and Bocchino, M. (2015). Levels of circulating endothelial cells are low in idiopathic pulmonary fibrosis and are further reduced by anti-fibrotic treatments. BMC Med., 13.","DOI":"10.1186\/s12916-015-0515-0"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s10456-012-9306-9","article-title":"Imbalance of circulating endothelial cells and progenitors in idiopathic pulmonary fibrosis","volume":"16","author":"Smadja","year":"2013","journal-title":"Angiogenesis"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1002\/art.27584","article-title":"2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology\/European League Against Rheumatism collaborative initiative","volume":"62","author":"Aletaha","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1164\/rccm.201308-1483ST","article-title":"An official American Thoracic Society\/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias","volume":"188","author":"Travis","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/S2213-2600(17)30433-2","article-title":"Diagnostic criteria for idiopathic pulmonary fibrosis: A Fleischner Society White Paper","volume":"6","author":"Lynch","year":"2018","journal-title":"Lancet Respir. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1136\/ard.2008.091918","article-title":"EULAR Scleroderma Trials and Research group statement and recommendations on endothelial precursor cells EUSTAR statement and recommendations on endothelial precursor cells","volume":"68","author":"Distler","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Schmidt-Lucke, C., Fichtlscherer, S., Aicher, A., Tsch\u00f6pe, C., Schultheiss, H.-P., Zeiher, A.M., and Dimmeler, S. (2010). Quantification of Circulating Endothelial Progenitor Cells Using the Modified ISHAGE Protocol. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013790"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1016\/j.ijcard.2012.10.047","article-title":"Quantification of circulating CD34 +\/KDR +\/CD45 dim endothelial progenitor cells: Analytical considerations","volume":"167","author":"Bruyndonckx","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8043792","DOI":"10.1155\/2016\/8043792","article-title":"Endothelial Progenitor Cells for Diagnosis and Prognosis in Cardiovascular Disease","volume":"2016","author":"Aragona","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1183\/09031936.00034810","article-title":"Circulating endothelial progenitor cells and chronic pulmonary diseases","volume":"37","author":"Huertas","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_21","first-page":"680","article-title":"Clinical and methodological aspects of endothelial function in patients with systemic autoimmune diseases","volume":"26","author":"Ghiadoni","year":"2008","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1016\/j.jacc.2004.12.074","article-title":"Impaired progenitor cell activity in age-related endothelial dysfunction","volume":"45","author":"Heiss","year":"2005","journal-title":"J. Am. Coll. Cardiol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/12\/4098\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:47:02Z","timestamp":1760179622000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/12\/4098"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,18]]},"references-count":22,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["jcm9124098"],"URL":"https:\/\/doi.org\/10.3390\/jcm9124098","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,18]]}}}