{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:52:01Z","timestamp":1790866321964,"version":"4.1.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ATVB"],"published-print":{"date-parts":[[1997,10]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            Exposure of vascular endothelial cells to fluid mechanical forces can modulate the expression of many genes involved in vascular physiology and pathophysiology. Here, we report that platelet-derived growth factor (PDGF) A-chain gene expression is induced at the level of transcription in cultured bovine aortic endothelial cells exposed to a physiologic level of steady laminar shear stress (10 dyn\/cm\n            <jats:sup>2<\/jats:sup>\n            ). 5\u2032 Deletion analysis of the human PDGF-A promoter revealed that a GC-rich region near the TATA box was required for shear-inducible reporter gene expression. This element conferred shear inducibility onto a heterologous promoter-reporter construct that was otherwise unresponsive to shear stress. The induction of PDGF-A expression by shear was preceded by rapid and transient induction in the expression of the immediate-early gene,\n            <jats:italic>egr-1<\/jats:italic>\n            , which binds to GC-rich sequences. Gel shift studies indicated that shear-induced Egr-1 bound to the proximal PDGF-A promoter in a specific and time-dependent manner, displacing Sp1 from their overlapping recognition elements. Overlapping consensus binding sites for Egr-1 and Sp1 also appear in the proximal promoters of several other endothelial genes, including transforming growth factor-\u03b2\n            <jats:sub>1<\/jats:sub>\n            and tissue factor, whose expression is modulated by shear stress. These findings define the Egr-1 binding site in the proximal PDGF-A promoter as a shear-stress-responsive element and suggest that shear-stimulated Egr-1 gene expression may be a unifying theme in the induction of various other endothelial genes exposed to biomechanical forces.\n          <\/jats:p>","DOI":"10.1161\/01.atv.17.10.2280","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T19:44:19Z","timestamp":1308339859000},"page":"2280-2286","source":"Crossref","is-referenced-by-count":158,"title":["Egr-1 is Activated in Endothelial Cells Exposed to Fluid Shear Stress and Interacts With a Novel Shear-Stress-Response Element in the PDGF A-Chain Promoter"],"prefix":"10.1161","volume":"17","author":[{"given":"Levon M.","family":"Khachigian","sequence":"first","affiliation":[{"name":"From the Vascular Research Division, Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith R.","family":"Anderson","sequence":"additional","affiliation":[{"name":"From the Vascular Research Division, Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy J.","family":"Halnon","sequence":"additional","affiliation":[{"name":"From the Vascular Research Division, Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Gimbrone","sequence":"additional","affiliation":[{"name":"From the Vascular Research Division, Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitzan","family":"Resnick","sequence":"additional","affiliation":[{"name":"From the Vascular Research Division, Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tucker","family":"Collins","sequence":"additional","affiliation":[{"name":"From the Vascular Research Division, Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.10.4591"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118106"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.1794"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117410"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.17.8069"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9290(95)00093-3"},{"key":"e_1_3_2_7_2","first-page":"H642","volume":"260","year":"1991","journal-title":"Am J Physiol."},{"key":"e_1_3_2_8_2","unstructured":"Halnon NJ Collins T Gimbrone MA Jr Resnick N. 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