{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T18:26:09Z","timestamp":1793730369908,"version":"4.6.1"},"reference-count":76,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["R01AG097492"],"award-info":[{"award-number":["R01AG097492"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015891","name":"AHA","doi-asserted-by":"publisher","award":["25POST1409853"],"award-info":[{"award-number":["25POST1409853"]}],"id":[{"id":"10.13039\/501100015891","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015891","name":"AHA","doi-asserted-by":"publisher","award":["R01HL150193"],"award-info":[{"award-number":["R01HL150193"]}],"id":[{"id":"10.13039\/501100015891","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To determine the endothelial-intrinsic role of TLR4 in inflammatory vascular remodelling and cytokine signalling, and to define how exogenous microbial and oxidation-derived endogenous signals are integrated by endothelial TLR4 to regulate vascular function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Single-cell transcriptomic analyses of human tissues identified endothelial cells as a coherent, lineage-consistent TLR4-expressing population across tissues and disease states, distinguishing TLR4 from other endothelial Toll-like receptors. Using tamoxifen-inducible endothelial-specific TLR4 knockout mice (Cdh5-CreERT2; Tlr4flox\/flox), we show that lack of TLR4 markedly impaired early venular remodelling, junctional loosening, vascular leakage, and neutrophil recruitment during skin wound healing, and suppressed tumour angiogenesis and growth in a syngeneic cancer model. Mechanistically, endothelial TLR4 activation induced a focused chemokine programme dominated by CXCL1\/2\/5\u2013CXCR2 signalling, promoting neutrophil recruitment and lipid-oxidation responses. Loss of endothelial TLR4 reduced myeloperoxidase (MPO)-positive inflammatory-cell accumulation and carboxyethylpyrrole lipid-peroxidation adduct deposition, supporting a feed-forward inflammatory loop in which neutrophil-derived oxidized lipids act as endogenous TLR4 ligands. Pharmacologic CXCR2 inhibition or combined ROS\/MPO suppression phenocopied endothelial TLR4 deletion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Endothelial-intrinsic TLR4 functions as a vascular inflammatory integrator that links microbial pattern recognition with endogenous oxidation-derived danger signalling to co-ordinate chemokine production, neutrophil recruitment, MPO-linked lipid-oxidation amplification, and angiogenesis. These findings identify endothelial TLR4 as a distinct and targetable vascular inflammatory node, functionally separable from haematopoietic TLR4, with implications for sterile inflammatory cardiovascular disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvag211","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:38:27Z","timestamp":1790077107000},"source":"Crossref","is-referenced-by-count":1,"title":["Endothelial TLR4 coordinates angiogenesis and inflammation through a CXCR2\u2013neutrophil\u2013oxidative axis"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6411-2322","authenticated-orcid":false,"given":"Iuliia","family":"Molokotina","sequence":"first","affiliation":[{"name":"Department of Genomic Sciences and Systems Biology, Cleveland Clinic Research , Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh","family":"Ford","sequence":"additional","affiliation":[{"name":"Department of Genomic Sciences and Systems Biology, Cleveland Clinic Research , Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olha","family":"Kyrychek","sequence":"additional","affiliation":[{"name":"Department of Genomic Sciences and Systems Biology, Cleveland Clinic Research , Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8596-3329","authenticated-orcid":false,"given":"Irina","family":"Zhevlakova","sequence":"additional","affiliation":[{"name":"Department of Genomic Sciences and Systems Biology, Cleveland Clinic Research , Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moses","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Genomic Sciences and Systems Biology, Cleveland Clinic Research , Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9550-6965","authenticated-orcid":false,"given":"Eugene A","family":"Podrez","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Cleveland Clinic Research, Cleveland Clinic , Cleveland, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5419-7865","authenticated-orcid":false,"given":"Anish","family":"Korrapati","sequence":"additional","affiliation":[{"name":"Department of Genomic Sciences and Systems Biology, Cleveland Clinic Research , Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0045-8102","authenticated-orcid":false,"given":"Olga A","family":"Cherepanova","sequence":"additional","affiliation":[{"name":"Department of Heart, Blood, and Kidney Research, Cleveland Clinic Research, Cleveland Clinic , Cleveland, OH ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2615-875X","authenticated-orcid":false,"given":"Tatiana V","family":"Byzova","sequence":"additional","affiliation":[{"name":"Department of Genomic Sciences and Systems Biology, Cleveland Clinic Research , Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"2026100723165910400_cvag211-B1","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1161\/01.RES.0000255691.76142.4a","article-title":"Phenotypic heterogeneity of the endothelium: I. 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