{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T11:08:06Z","timestamp":1764155286392,"version":"3.46.0"},"reference-count":81,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,1,11]],"date-time":"2025-01-11T00:00:00Z","timestamp":1736553600000},"content-version":"vor","delay-in-days":77,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000296","name":"British Skin Foundation","doi-asserted-by":"publisher","award":["016\/s\/17 \/ R122088"],"award-info":[{"award-number":["016\/s\/17 \/ R122088"]}],"id":[{"id":"10.13039\/501100000296","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Vascular endothelial growth factor A (VEGF-A)-mediated angiogenesis is involved in the pathogenesis of psoriasis. VEGF-A inhibitors are widely used to treat oncological and ophthalmological diseases but have not been used in psoriasis management. The molecular mechanisms underlying the effects of VEGF-A inhibition in psoriatic skin remain unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To identify the genes and canonical pathways affected by VEGF-A inhibition in non-lesional and plaque skin ex vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Total RNA sequencing was performed on skin biopsies from patients with psoriasis (n = 6; plaque and non-lesional skin) and healthy controls (n = 6) incubated with anti-VEGF-A monoclonal antibody (bevacizumab, Avastin\u00ae) or human IgG1 isotype control for 12 h in serum-free organ culture. Differentially expressed genes between paired control and treated samples with adjusted p-values &amp;lt;0.1 were considered significant. Gene ontology and ingenuity pathway analysis was used to identify enriched biological processes, canonical pathways and upstream regulators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>VEGF-A inhibition upregulated the expression of genes involved in lipid metabolism. Pathway enrichment analysis identified the activation of pathways involved in fatty acids and lipid biosynthesis and degradation in non-lesional skin and ferroptosis in plaque skin. VEGF-A inhibition downregulated endothelial cell apoptosis in non-lesional psoriasis skin and members of the interferon family were identified as potential regulators of the effects of VEGF-A inhibition in non-lesional skin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Early response to VEGF-A inhibition is associated with changes in lipid metabolism in non-lesional psoriasis skin and cellular stress in psoriasis plaque. More investigation is needed to validate these findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ski2.471","type":"journal-article","created":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T15:23:55Z","timestamp":1729956235000},"source":"Crossref","is-referenced-by-count":0,"title":["Vascular Endothelial Growth Factor a Inhibition Remodels the Transcriptional Signature of Lipid Metabolism in Psoriasis Non-Lesional Skin in 12 H Ex Vivo Culture"],"prefix":"10.1093","volume":"4","author":[{"given":"Andrea","family":"Luengas-Martinez","sequence":"first","affiliation":[{"name":"Centre for Dermatology Research and Manchester Academic Health Science Centre, The University of Manchester , Manchester ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dina","family":"Ismail","sequence":"additional","affiliation":[{"name":"Centre for Dermatology Research and Manchester Academic Health Science Centre, The University of Manchester , Manchester 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