Glucocorticoid-mediated inhibition of angiogenic changes in human endothelial cells is not caused by reductions in cell proliferation or migration
Glucocorticoid-mediated inhibition of angiogenesis is important in physiology, pathophysiology and therapy. However, the mechanisms through which glucocorticoids inhibit growth of new blood vessels have not been established. This study addresses the hypothesis that physiological levels of glucocorti...
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| description | Glucocorticoid-mediated inhibition of angiogenesis is important in physiology, pathophysiology and therapy. However, the mechanisms through which glucocorticoids inhibit growth of new blood vessels have not been established. This study addresses the hypothesis that physiological levels of glucocorticoids inhibit angiogenesis by directly preventing tube formation by endothelial cells.
Cultured human umbilical vein (HUVEC) and aortic (HAoEC) endothelial cells were used to determine the influence of glucocorticoids on tube-like structure (TLS) formation, and on cellular proliferation (5-bromo-2'-deoxyuridine (BrdU) incorporation), viability (ATP production) and migration (Boyden chambers). Dexamethasone or cortisol (at physiological concentrations) inhibited both basal and prostaglandin F(2α) (PGF(2α))-induced and vascular endothelial growth factor (VEGF) stimulated TLS formation in endothelial cells (ECs) cultured on Matrigel, effects which were blocked with the glucocorticoid receptor antagonist RU38486. Glucocorticoids had no effect on EC viability, migration or proliferation. Time-lapse imaging showed that cortisol blocked VEGF-stimulated cytoskeletal reorganisation and initialisation of tube formation. Real time PCR suggested that increased expression of thrombospodin-1 contributed to glucocorticoid-mediated inhibition of TLS formation.
We conclude that glucocorticoids interact directly with glucocorticoid receptors on vascular ECs to inhibit TLS formation. This action, which was conserved in ECs from two distinct vascular territories, was due to alterations in cell morphology rather than inhibition of EC viability, migration or proliferation and may be mediated in part by induction of thrombospodin-1. These findings provide important insights into the anti-angiogenic action of endogenous glucocorticoids in health and disease. |
| doi_str_mv | 10.1371/journal.pone.0014476 |
| format | Article |
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Cultured human umbilical vein (HUVEC) and aortic (HAoEC) endothelial cells were used to determine the influence of glucocorticoids on tube-like structure (TLS) formation, and on cellular proliferation (5-bromo-2'-deoxyuridine (BrdU) incorporation), viability (ATP production) and migration (Boyden chambers). Dexamethasone or cortisol (at physiological concentrations) inhibited both basal and prostaglandin F(2α) (PGF(2α))-induced and vascular endothelial growth factor (VEGF) stimulated TLS formation in endothelial cells (ECs) cultured on Matrigel, effects which were blocked with the glucocorticoid receptor antagonist RU38486. Glucocorticoids had no effect on EC viability, migration or proliferation. Time-lapse imaging showed that cortisol blocked VEGF-stimulated cytoskeletal reorganisation and initialisation of tube formation. Real time PCR suggested that increased expression of thrombospodin-1 contributed to glucocorticoid-mediated inhibition of TLS formation.
We conclude that glucocorticoids interact directly with glucocorticoid receptors on vascular ECs to inhibit TLS formation. This action, which was conserved in ECs from two distinct vascular territories, was due to alterations in cell morphology rather than inhibition of EC viability, migration or proliferation and may be mediated in part by induction of thrombospodin-1. These findings provide important insights into the anti-angiogenic action of endogenous glucocorticoids in health and disease.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0014476</identifier><identifier>PMID: 21217824</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Angiogenesis ; Aorta ; Aorta - cytology ; Blood vessels ; Bromodeoxyuridine - pharmacology ; Cardiovascular Disorders/Cardiovascular Pharmacology ; Cardiovascular Disorders/Vascular Biology ; Cell adhesion & migration ; Cell morphology ; Cell Movement ; Cell Proliferation ; Cell Survival ; Cellular manufacture ; Cellular structure ; Collagen - chemistry ; Cortisol ; Cytokines ; Cytology ; Cytoskeleton ; Dexamethasone ; Diabetes ; Diabetes and Endocrinology/Endocrinology ; Drug Combinations ; Endothelial cells ; Endothelial Cells - cytology ; Endothelium ; Glucocorticoid receptors ; Glucocorticoids ; Glucocorticoids - chemistry ; Heart attacks ; Humans ; Hydrocortisone - metabolism ; Inhibition ; Laboratories ; Laminin - chemistry ; Medical research ; Mifepristone - pharmacology ; Neovascularization ; Neovascularization, Pathologic ; Physiology ; Proteoglycans - chemistry ; Receptors ; Reverse Transcriptase Polymerase Chain Reaction ; Science ; Steroids (Organic compounds) ; Thrombospondin 1 - biosynthesis ; Umbilical vein ; Umbilical Veins - cytology ; Vascular endothelial growth factor ; Viability ; Wound healing</subject><ispartof>PloS one, 2010-12, Vol.5 (12), p.e14476</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Logie et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Logie et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-567ef42fc765e96e316c248c3f09309c5c46886b86dc96c5fd79116d0edb317d3</citedby><cites>FETCH-LOGICAL-c691t-567ef42fc765e96e316c248c3f09309c5c46886b86dc96c5fd79116d0edb317d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013101/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013101/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21217824$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Reitsma, Pieter H.</contributor><creatorcontrib>Logie, James J</creatorcontrib><creatorcontrib>Ali, Sadaf</creatorcontrib><creatorcontrib>Marshall, Kathryn M</creatorcontrib><creatorcontrib>Heck, Margarete M S</creatorcontrib><creatorcontrib>Walker, Brian R</creatorcontrib><creatorcontrib>Hadoke, Patrick W F</creatorcontrib><title>Glucocorticoid-mediated inhibition of angiogenic changes in human endothelial cells is not caused by reductions in cell proliferation or migration</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Glucocorticoid-mediated inhibition of angiogenesis is important in physiology, pathophysiology and therapy. However, the mechanisms through which glucocorticoids inhibit growth of new blood vessels have not been established. This study addresses the hypothesis that physiological levels of glucocorticoids inhibit angiogenesis by directly preventing tube formation by endothelial cells.
Cultured human umbilical vein (HUVEC) and aortic (HAoEC) endothelial cells were used to determine the influence of glucocorticoids on tube-like structure (TLS) formation, and on cellular proliferation (5-bromo-2'-deoxyuridine (BrdU) incorporation), viability (ATP production) and migration (Boyden chambers). Dexamethasone or cortisol (at physiological concentrations) inhibited both basal and prostaglandin F(2α) (PGF(2α))-induced and vascular endothelial growth factor (VEGF) stimulated TLS formation in endothelial cells (ECs) cultured on Matrigel, effects which were blocked with the glucocorticoid receptor antagonist RU38486. Glucocorticoids had no effect on EC viability, migration or proliferation. Time-lapse imaging showed that cortisol blocked VEGF-stimulated cytoskeletal reorganisation and initialisation of tube formation. Real time PCR suggested that increased expression of thrombospodin-1 contributed to glucocorticoid-mediated inhibition of TLS formation.
We conclude that glucocorticoids interact directly with glucocorticoid receptors on vascular ECs to inhibit TLS formation. This action, which was conserved in ECs from two distinct vascular territories, was due to alterations in cell morphology rather than inhibition of EC viability, migration or proliferation and may be mediated in part by induction of thrombospodin-1. 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However, the mechanisms through which glucocorticoids inhibit growth of new blood vessels have not been established. This study addresses the hypothesis that physiological levels of glucocorticoids inhibit angiogenesis by directly preventing tube formation by endothelial cells.
Cultured human umbilical vein (HUVEC) and aortic (HAoEC) endothelial cells were used to determine the influence of glucocorticoids on tube-like structure (TLS) formation, and on cellular proliferation (5-bromo-2'-deoxyuridine (BrdU) incorporation), viability (ATP production) and migration (Boyden chambers). Dexamethasone or cortisol (at physiological concentrations) inhibited both basal and prostaglandin F(2α) (PGF(2α))-induced and vascular endothelial growth factor (VEGF) stimulated TLS formation in endothelial cells (ECs) cultured on Matrigel, effects which were blocked with the glucocorticoid receptor antagonist RU38486. Glucocorticoids had no effect on EC viability, migration or proliferation. Time-lapse imaging showed that cortisol blocked VEGF-stimulated cytoskeletal reorganisation and initialisation of tube formation. Real time PCR suggested that increased expression of thrombospodin-1 contributed to glucocorticoid-mediated inhibition of TLS formation.
We conclude that glucocorticoids interact directly with glucocorticoid receptors on vascular ECs to inhibit TLS formation. This action, which was conserved in ECs from two distinct vascular territories, was due to alterations in cell morphology rather than inhibition of EC viability, migration or proliferation and may be mediated in part by induction of thrombospodin-1. These findings provide important insights into the anti-angiogenic action of endogenous glucocorticoids in health and disease.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21217824</pmid><doi>10.1371/journal.pone.0014476</doi><tpages>e14476</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Angiogenesis Aorta Aorta - cytology Blood vessels Bromodeoxyuridine - pharmacology Cardiovascular Disorders/Cardiovascular Pharmacology Cardiovascular Disorders/Vascular Biology Cell adhesion & migration Cell morphology Cell Movement Cell Proliferation Cell Survival Cellular manufacture Cellular structure Collagen - chemistry Cortisol Cytokines Cytology Cytoskeleton Dexamethasone Diabetes Diabetes and Endocrinology/Endocrinology Drug Combinations Endothelial cells Endothelial Cells - cytology Endothelium Glucocorticoid receptors Glucocorticoids Glucocorticoids - chemistry Heart attacks Humans Hydrocortisone - metabolism Inhibition Laboratories Laminin - chemistry Medical research Mifepristone - pharmacology Neovascularization Neovascularization, Pathologic Physiology Proteoglycans - chemistry Receptors Reverse Transcriptase Polymerase Chain Reaction Science Steroids (Organic compounds) Thrombospondin 1 - biosynthesis Umbilical vein Umbilical Veins - cytology Vascular endothelial growth factor Viability Wound healing |
| title | Glucocorticoid-mediated inhibition of angiogenic changes in human endothelial cells is not caused by reductions in cell proliferation or migration |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T06%3A07%3A56IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Glucocorticoid-mediated%20inhibition%20of%20angiogenic%20changes%20in%20human%20endothelial%20cells%20is%20not%20caused%20by%20reductions%20in%20cell%20proliferation%20or%20migration&rft.jtitle=PloS%20one&rft.au=Logie,%20James%20J&rft.date=2010-12-31&rft.volume=5&rft.issue=12&rft.spage=e14476&rft.pages=e14476-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0014476&rft_dat=%3Cgale_plos_%3EA473807794%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1296217932&rft_id=info:pmid/21217824&rft_galeid=A473807794&rft_doaj_id=oai_doaj_org_article_c99b08510d6645a3837ab9ee019660f9&rfr_iscdi=true |