{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T13:58:57Z","timestamp":1783778337347,"version":"3.55.0"},"reference-count":47,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100008604","name":"Scleroderma and Raynaud\u2019s UK","doi-asserted-by":"publisher","award":["BA9"],"award-info":[{"award-number":["BA9"]}],"id":[{"id":"10.13039\/501100008604","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Scleroderma and Related Disorders"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>The objective of the study is to explore the pathogenic relationship between vasculopathy and fibrosis in systemic sclerosis through expression of vascular biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Plasma biomarkers including panVEGF-A, VEGF-A\n                      <jats:sub>165<\/jats:sub>\n                      b and angiopoietins (Ang) and clinical parameters were investigated in 53 systemic sclerosis patients and 15 controls. Biopsies of affected skin from 10 systemic sclerosis patients and 5 controls were used to assess expression of hypoxia-inducible factor (HIF1\u03b1, -2\u03b1) and VEGF-A isoforms. Vasculopathy was assessed using nailfold capillaroscopy (qualitative pattern and intercapillary distance), reperfusion gradient after ischaemic challenge and ultrasound vascularity index (dorsovolar vascularity index). Skin fibrosis was assessed using skin scores and ultrasound (skin thickness, echogenicity and elastography).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Plasma Ang-2 was increased (p\u2009=\u20090.012) and Ang-1\/-2 ratio reduced (p\u2009=\u20090.018) in systemic sclerosis patients compared to controls. Ang-2 progressively increased across nailfold capillaroscopy patterns (p\u2009=\u20090.031) and weakly correlated with intercapillary distance (+0.284, p\u2009=\u20090.05) and reperfusion gradient (\u22120.356, p\u2009=\u20090.018). Plasma angiopoietins correlated with echogenicity (Ang-1 +0.381, p\u2009=\u20090.006; Ang-2 +0.330, p\u2009=\u20090.022) and elastography (Ang-2 +0.353, p\u2009=\u20090.014). Plasma VEGF-A\n                      <jats:sub>165<\/jats:sub>\n                      b correlated with dorsovolar vascularity index (\u22120.289, p\u2009=\u20090.039). HIF1\u03b1 and 2\u03b1 were increased in skin (p\u2009=\u20090.008) with HIF2\u03b1 predominance. Epidermal HIF2\u03b1 correlated more strongly with VEGF-A\n                      <jats:sub>165<\/jats:sub>\n                      b (+0.709, p\u2009=\u20090.022) than panVEGF-A (+0.552, p\u2009=\u20090.098). Epidermal HIF2\u03b1 and fibroblast VEGF-A\n                      <jats:sub>165<\/jats:sub>\n                      b tended to associate with early and diffuse cutaneous systemic sclerosis. Cutaneous expression of HIF1\u03b1 (+0.489, p\u2009=\u20090.069) and HIF2\u03b1 (+0.489, p\u2009=\u20090.064) correlated with intercapillary distance. Epidermal VEGF-A\n                      <jats:sub>165<\/jats:sub>\n                      b correlated with skin thickness (\u22120.672, p\u2009=\u20090.006).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Increased expression of HIF\u03b1 and antiangiogenic biomarkers associated with both vasculopathy and fibrosis in systemic sclerosis. Our data highlight the conceivable therapeutic targets of dual inhibitory biomarkers such as Ang-2.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/23971983251344040","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T06:49:45Z","timestamp":1748933385000},"page":"413-424","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Examining the relationship between vascular biomarkers and both microangiopathy and cutaneous fibrosis in systemic sclerosis"],"prefix":"10.1136","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6221-589X","authenticated-orcid":false,"given":"Victoria Anne","family":"Flower","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Royal National Hospital for Rheumatic Diseases, Royal United Hospitals Bath NHS Foundation Trust, Bath, UK"},{"name":"Department of Life Sciences, University of Bath, Bath, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaney Louise","family":"Barratt","sequence":"additional","affiliation":[{"name":"Bristol Interstitial Lung Disease Service, Department of Respiratory Medicine, North Bristol NHS Trust, Bristol, UK"},{"name":"Academic Respiratory Unit, School of Clinical Sciences, University of Bristol, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren John","family":"Hart","sequence":"additional","affiliation":[{"name":"Clinical Measurement and Imaging Department, Royal National Hospital for Rheumatic Diseases, Royal United Hospitals Bath NHS Foundation Trust, Bath, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline Anne","family":"Shipley","sequence":"additional","affiliation":[{"name":"Clinical Measurement and Imaging Department, Royal National Hospital for Rheumatic Diseases, Royal United Hospitals Bath NHS Foundation Trust, Bath, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John David","family":"Pauling","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, North Bristol NHS Trust, Bristol, UK"},{"name":"Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,6,3]]},"reference":[{"issue":"4","key":"e_1_3_3_2_2","first-page":"82","article-title":"From VEDOSS to established systemic sclerosis diagnosis according to ACR\/EULAR 2013 classification criteria: a French-Italian capillaroscopic survey","author":"Vasile M","year":"2018","unstructured":"Vasile M, Avouac J, Sciarra I, et al. From VEDOSS to established systemic sclerosis diagnosis according to ACR\/EULAR 2013 classification criteria: a French-Italian capillaroscopic survey. 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