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Med."],"abstract":"<jats:p>Systemic Sclerosis (SSc) is an autoimmune disease marked by dysregulation of the immune system, tissue fibrosis and dysfunction of the vasculature. Vascular damage, remodeling and inadequate endothelial repair are hallmarks of the disease. Since early stages of SSc, damage and apoptosis of endothelial cells (ECs) can lead to perivascular inflammation, oxidative stress and tissue hypoxia, resulting in multiple clinical manifestations. Raynaud's phenomenon, edematous puffy hands, digital ulcers, pulmonary artery hypertension, erectile dysfunction, scleroderma renal crisis and heart involvement severely affect quality of life and survival. Understanding pathogenic aspects and biomarkers that reflect endothelial damage in SSc is essential to guide therapeutic interventions. Treatment approaches described for SSc-associated vasculopathy include pharmacological options to improve blood flow and tissue perfusion and, more recently, cellular therapy to enhance endothelial repair, promote angiogenesis and heal injuries. This mini-review examines the current knowledge on cellular and molecular aspects of SSc vasculopathy, as well as established and developing therapeutic approaches for improving the vascular compartment.<\/jats:p>","DOI":"10.3389\/fmed.2021.788250","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T05:42:53Z","timestamp":1640151773000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":50,"title":["Management of Endothelial Dysfunction in Systemic Sclerosis: Current and Developing Strategies"],"prefix":"10.3389","volume":"8","author":[{"given":"Dj\u00falio C\u00e9sar","family":"Zanin-Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maynara","family":"Santana-Gon\u00e7alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna Yumi","family":"Kawashima-Vasconcelos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carolina","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/978-3-319-98477-3_4","article-title":"Vascular mechanisms of systemic sclerosis","volume-title":"Atlas of Ulcers in Systemic Sclerosis","author":"Schniering","year":"2019"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1016\/S0140-6736(17)30933-9","article-title":"Systemic sclerosis","volume":"390","author":"Denton","year":"2017","journal-title":"Lancet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1177\/2397198319833486","article-title":"Nailfold capillaroscopy in systemic sclerosis \u2013 state of the art: the evolving knowledge about capillaroscopic abnormalities in systemic sclerosis","volume":"4","author":"Lambova","year":"2019","journal-title":"J Scleroderma Relat Disord."},{"key":"B4","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1080\/10408363.2017.1394267","article-title":"The vascular endothelium: a regulator of arterial tone and interface for the immune system","volume":"54","author":"Khaddaj Mallat","year":"2017","journal-title":"Crit Rev Clin Lab Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/s00281-015-0505-5","article-title":"Vasculopathy in scleroderma","volume":"37","author":"Asano","year":"2015","journal-title":"Semin Immunopathol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.1002\/art.37988","article-title":"Review: evidence that systemic sclerosis is a vascular disease","volume":"65","author":"Matucci-Cerinic","year":"2013","journal-title":"Arthritis Rheum."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1165\/rcmb.2009-0388TR","article-title":"Endothelin in pulmonary fibrosis","volume":"44","author":"Fonseca","year":"2011","journal-title":"Am J Respir Cell Mol Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/ar2186","article-title":"How does endothelial cell injury start? 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