{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T14:41:56Z","timestamp":1783694516164,"version":"3.55.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2008,5,23]]},"abstract":"<jats:p>\n            Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is activated by reduced endothelial shear stress and stimulates smooth muscle cell proliferation in vitro. Moreover, HB-EGF is augmented at sites of intimal hyperplasia and atherosclerosis, conditions favored by low\/disturbed shear stress. We thus tested whether HB-EGF contributes to low flow-induced negative hypertrophic remodeling (FINR) of a mouse carotid artery. Blood flow was surgically decreased in the left and increased in the right common carotid arteries. After 21 days, the left carotid artery exhibited lumen narrowing, thickening of intima\u2013media and adventitia, and increased circumference that were inhibited by \u224850% in HB-EGF\n            <jats:sup>+\/\u2212<\/jats:sup>\n            and \u224890% in HB-EGF\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice. FINR was also inhibited by the EGF receptor inhibitor AG1478. In contrast, eutrophic outward remodeling of the right carotid artery was unaffected in HB-EGF\n            <jats:sup>+\/\u2212<\/jats:sup>\n            and HB-EGF\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice, nor by AG1478. FINR-induced proliferation and leukocyte accumulation were reduced in HB-EGF\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            . FINR was associated with increased reactive oxygen species, increased expression of pro-HB-EGF and tumor necrosis factor \u03b1\u2013converting enzyme (pro-HB-EGF sheddase), increased phosphorylation of EGF receptor and extracellular signal-regulated kinase 1\/2, and increased nuclear factor \u03baB activity. Apocynin and deletion of p47\n            <jats:sup>phox<\/jats:sup>\n            inhibited FINR, whereas deletion of HB-EGF abolished nuclear factor \u03baB activation in smooth muscle cells. These findings suggest that HB-EGF signaling is required for low flow-induced hypertrophic remodeling and may participate in vascular wall disease and remodeling.\n          <\/jats:p>","DOI":"10.1161\/circresaha.108.171728","type":"journal-article","created":{"date-parts":[[2008,4,25]],"date-time":"2008-04-25T01:37:18Z","timestamp":1209087438000},"page":"1275-1285","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":40,"title":["Heparin-Binding Epidermal Growth Factor\u2013Like Growth Factor Signaling in Flow-Induced Arterial Remodeling"],"prefix":"10.1161","volume":"102","author":[{"given":"Hua","family":"Zhang","sequence":"first","affiliation":[{"name":"From the Departments of Cell &amp; Molecular Physiology (H.Z., K.K.M., J.E.F.) and Biochemistry &amp; Biophysics (S.W.S.), University of North Carolina, Chapel Hill; Ludwig Institute for Cancer Research (T.G.J.), Heidelberg, Australia; and University of Georgia (D.C.L.), Athens."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan W.","family":"Sunnarborg","sequence":"additional","affiliation":[{"name":"From the Departments of Cell &amp; Molecular Physiology (H.Z., K.K.M., J.E.F.) and Biochemistry &amp; Biophysics (S.W.S.), University of North Carolina, Chapel Hill; Ludwig Institute for Cancer Research (T.G.J.), Heidelberg, Australia; and University of Georgia (D.C.L.), Athens."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Kirk","family":"McNaughton","sequence":"additional","affiliation":[{"name":"From the Departments of Cell &amp; Molecular Physiology (H.Z., K.K.M., J.E.F.) and Biochemistry &amp; Biophysics (S.W.S.), University of North Carolina, Chapel Hill; Ludwig Institute for Cancer Research (T.G.J.), Heidelberg, Australia; and University of Georgia (D.C.L.), Athens."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terrance G.","family":"Johns","sequence":"additional","affiliation":[{"name":"From the Departments of Cell &amp; Molecular Physiology (H.Z., K.K.M., J.E.F.) and Biochemistry &amp; Biophysics (S.W.S.), University of North Carolina, Chapel Hill; Ludwig Institute for Cancer Research (T.G.J.), Heidelberg, Australia; and University of Georgia (D.C.L.), Athens."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Lee","sequence":"additional","affiliation":[{"name":"From the Departments of Cell &amp; Molecular Physiology (H.Z., K.K.M., J.E.F.) and Biochemistry &amp; Biophysics (S.W.S.), University of North Carolina, Chapel Hill; Ludwig Institute for Cancer Research (T.G.J.), Heidelberg, Australia; and University of Georgia (D.C.L.), Athens."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Faber","sequence":"additional","affiliation":[{"name":"From the Departments of Cell &amp; Molecular Physiology (H.Z., K.K.M., J.E.F.) and Biochemistry &amp; Biophysics (S.W.S.), University of North Carolina, Chapel Hill; Ludwig Institute for Cancer Research (T.G.J.), Heidelberg, Australia; and University of Georgia (D.C.L.), Athens."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.102.10.1186"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00035.2004"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700215"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2006.02.005"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001573-200311000-00007"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.106.634378"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000223322.16149.9a"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2005.030098"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000023230.17493.e3"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000134958.88379.2e"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27100"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000229657.83816.a7"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00129.2005"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000147962.01036.bb"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000216428.90962.60"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112050200"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2005.08.031"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2005.06.038"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.2469"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2005.02.027"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.16.12.1524"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1067\/mva.2003.92"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000236203.90331.d0"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.5551\/jat.12.73"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2004.03.028"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.94.11.2778"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2036503100"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0537588100"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg264"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000175761.59602.16"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700282"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00535.2005"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000181759.63239.21"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2006.04.011"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00464.2001"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2004.06.008"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.00-0371fje"},{"key":"e_1_3_3_38_2","first-page":"49","volume":"11","year":"2003","unstructured":"Nishi H, Neta G, Nishi KH, Akers LM, Rikiyama T, Proctor KN, Murphy BA, Johnson AC. Analysis of the epidermal growth factor receptor promoter: the effect of nuclear factor-kappaB. 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