{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:40:07Z","timestamp":1791168007846,"version":"4.1.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2009,9,25]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Rationale:<\/jats:italic>\n            <\/jats:bold>\n            Prostaglandin (PG)E\n            <jats:sub>2<\/jats:sub>\n            exerts temporally distinct actions on blood vessels, immediate vasodilatation, and long-term activation of angiogenesis.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Objective:<\/jats:italic>\n            <\/jats:bold>\n            To study the mechanism of PGE\n            <jats:sub>2<\/jats:sub>\n            induction of angiogenesis, we characterized its effect on fibroblast growth factor (FGF)-2 signaling in cultured endothelial cells and in ex vivo and in vivo assays of blood vessel formation.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results:<\/jats:italic>\n            <\/jats:bold>\n            Using Western blotting assay, we demonstrated that PGE\n            <jats:sub>2<\/jats:sub>\n            induced upregulation of components of the FGF-2 pathway: FGF-2 protein, phosphorylation of FGF receptor type 1 (FGFR1), activation of FRS2\u03b1 (FGFR substrate 2\u03b1), phospholipase C\u03b3, endothelial nitric oxide synthase, extracellular signal-regulated kinase 1\/2, and the transcription factor STAT-3. Synergism between PGE\n            <jats:sub>2<\/jats:sub>\n            and FGF-2 promoted endothelial cell proliferation and robust angiogenesis in vivo, in rabbit cornea and Matrigel assays. The magnitude of the angiogenic response to PGE\n            <jats:sub>2<\/jats:sub>\n            was directly related to FGF-2 availability which determined the extent of FGFR1 activation. In fact, PGE\n            <jats:sub>2<\/jats:sub>\n            induction of angiogenesis in vitro was impaired in FGF-2\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            endothelial cells and FGFR1 blockade abrogated PGE\n            <jats:sub>2<\/jats:sub>\n            action on the endothelium, preventing the activation of FGF-2 signaling.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusion:<\/jats:italic>\n            <\/jats:bold>\n            We propose a model for the angiogenic switch based on the autocrine\/paracrine FGF-2\/FGFR1 activation by PGE\n            <jats:sub>2<\/jats:sub>\n            and FGF-2 synergistic interaction. The synergism between the PGE\n            <jats:sub>2<\/jats:sub>\n            and FGF-2 signaling pathways here described may explain the mechanism of action of drug combinations, the most notable being cyclooxygenase inhibitors with growth factors or growth factor receptor inhibitors.\n          <\/jats:p>","DOI":"10.1161\/circresaha.109.203760","type":"journal-article","created":{"date-parts":[[2009,8,28]],"date-time":"2009-08-28T02:07:14Z","timestamp":1251425234000},"page":"657-666","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":46,"title":["Prostaglandin E\n            <sub>2<\/sub>\n            Primes the Angiogenic Switch via a Synergic Interaction With the Fibroblast Growth Factor-2 Pathway"],"prefix":"10.1161","volume":"105","author":[{"given":"Federica","family":"Finetti","sequence":"first","affiliation":[{"name":"From the Department of Molecular Biology, University of Siena; and Istituto Toscano Tumori, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Donnini","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Biology, University of Siena; and Istituto Toscano Tumori, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Giachetti","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Biology, University of Siena; and Istituto Toscano Tumori, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Morbidelli","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Biology, University of Siena; and Istituto Toscano Tumori, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Ziche","sequence":"additional","affiliation":[{"name":"From the Department of Molecular Biology, University of Siena; and Istituto Toscano Tumori, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","first-page":"213","volume":"88","year":"1937","unstructured":"von Euler US. 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