{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T12:52:32Z","timestamp":1780491152090,"version":"3.54.1"},"reference-count":47,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,1,1]]},"abstract":"<jats:p>Epi dermal growth factor (EGF) receptor (EGFR) is activated by its canonical ligands and transactivated by various vasoactive substances, e.g. angiotensin II (Ang II). Vascular EGFR has been proposed to be involved in vascular tissue homoeostasis and remodelling. Thus, most studies have focused on its role during long-term vascular changes whereas the relevance for acute regulation of vascular function in\u00a0vivo and ex vivo is insufficiently understood. To investigate the postnatal role of VSMCs (vascular smooth muscle cells) EGFR in\u00a0vivo and ex vivo, we generated a mouse model with cell-specific and inducible deletion of VSMC EGFR and studied the effect on basal blood pressure, acute pressure response to, among others, Ang II in\u00a0vivo as well as ex vivo, cardiovascular tissue homoeostasis and vessel morphometry in male mice. In knockout (KO) animals, systolic, diastolic and mean blood pressures were reduced compared with wild-type (WT). Furthermore, Ang II-induced pressure load was lower in KO animals, as was Ang II-induced force development and extracellular-signal-regulated kinase 1 and 2 (ERK1\/2) phosphorylation in aortic rings from KO animals. By contrast, we observed no difference in force development during application of serotonin, KCl, endothelin-1 or endothelin-1-induced pressure load in KO animals. In addition, nitric oxide (NO)-mediated vasodilation was not affected. Heart weight (HW) increase and up-regulation of aortic and cardiac expression of Ccl2 (chemoattractant protein-2) and serpinE1 (plasminogen activator inhibitor 1) during the transition from 4- to 10-months of age were prevented by VSMC EGFR KO. We conclude that VSMC EGFR is involved in basal blood pressure homoeostasis and acute pressure response to Ang II, and thereby contributes to maturation-related remodelling.<\/jats:p>","DOI":"10.1042\/cs20150503","type":"journal-article","created":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T01:48:58Z","timestamp":1444096138000},"page":"19-33","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Consequences of postnatal vascular smooth muscle EGFR deletion on acute angiotensin II action"],"prefix":"10.1042","volume":"130","author":[{"given":"Barbara","family":"Schreier","sequence":"first","affiliation":[{"name":"Julius-Bernstein-Institute of Physiology, Martin Luther University Halle-Wittenberg, 06112 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirja","family":"H\u00fcnerberg","sequence":"additional","affiliation":[{"name":"Julius-Bernstein-Institute of Physiology, Martin Luther University Halle-Wittenberg, 06112 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sindy","family":"Rabe","sequence":"additional","affiliation":[{"name":"Julius-Bernstein-Institute of Physiology, Martin Luther University Halle-Wittenberg, 06112 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid","family":"Mildenberger","sequence":"additional","affiliation":[{"name":"Julius-Bernstein-Institute of Physiology, Martin Luther University Halle-Wittenberg, 06112 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Bethmann","sequence":"additional","affiliation":[{"name":"Julius-Bernstein-Institute of Physiology, Martin Luther University Halle-Wittenberg, 06112 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Heise","sequence":"additional","affiliation":[{"name":"Julius-Bernstein-Institute of Physiology, Martin Luther University Halle-Wittenberg, 06112 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Sibilia","sequence":"additional","affiliation":[{"name":"Institute of Cancer Research, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Offermanns","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gekle","sequence":"additional","affiliation":[{"name":"Julius-Bernstein-Institute of Physiology, Martin Luther University Halle-Wittenberg, 06112 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2015,11,30]]},"reference":[{"key":"2021113010393881800_B1","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/S0955-0674(99)80024-6","article-title":"Epidermal growth factor receptors: critical mediators of multiple receptor pathways","volume":"11","author":"Hackel","year":"1999","journal-title":"Curr. Opin. Cell Biol."},{"key":"2021113010393881800_B2","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/35052073","article-title":"Untangling the ErbB signalling network","volume":"2","author":"Yarden","year":"2001","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2021113010393881800_B3","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/S0014-4827(02)00105-2","article-title":"EGF receptor ligands","volume":"284","author":"Harris","year":"2003","journal-title":"Exp. Cell Res."},{"key":"2021113010393881800_B4","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1038\/47260","article-title":"EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF","volume":"402","author":"Prenzel","year":"1999","journal-title":"Nature"},{"key":"2021113010393881800_B5","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/S0092-8674(02)00966-2","article-title":"Ligand-induced, receptor-mediated dimerization and activation of EGF receptor","volume":"110","author":"Schlessinger","year":"2002","journal-title":"Cell"},{"key":"2021113010393881800_B6","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1161\/HYPERTENSIONAHA.112.196543","article-title":"Loss of epidermal growth factor receptor in vascular smooth muscle cells and cardiomyocytes causes arterial hypotension and cardiac hypertrophy","volume":"61","author":"Schreier","year":"2013","journal-title":"Hypertension"},{"key":"2021113010393881800_B7","doi-asserted-by":"publisher","first-page":"e30156","DOI":"10.1371\/journal.pone.0030156","article-title":"The epidermal growth factor receptor is involved in angiotensin II but not aldosterone\/salt-induced cardiac remodelling","volume":"7","author":"Messaoudi","year":"2012","journal-title":"PLoS One"},{"key":"2021113010393881800_B8","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1161\/01.CIR.0000030181.63741.56","article-title":"Angiotensin II-induced cardiac hypertrophy and hypertension are attenuated by epidermal growth factor receptor antisense","volume":"106","author":"Kagiyama","year":"2002","journal-title":"Circulation"},{"key":"2021113010393881800_B9","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1161\/HYPERTENSIONAHA.115.05344","article-title":"Role of epidermal growth factor receptor and endoplasmic reticulum stress in vascular remodeling induced by angiotensin II","volume":"65","author":"Takayanagi","year":"2015","journal-title":"Hypertension"},{"key":"2021113010393881800_B10","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1172\/JCI31901","article-title":"Beta-arrestin-mediated beta1-adrenergic receptor transactivation of the EGFR confers cardioprotection","volume":"117","author":"Noma","year":"2007","journal-title":"J. Clin. Invest."},{"key":"2021113010393881800_B11","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1111\/j.1476-5381.2010.00829.x","article-title":"alpha1-Adrenoceptor-mediated contraction of rat aorta is partly mediated via transactivation of the epidermal growth factor receptor","volume":"161","author":"Ulu","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"2021113010393881800_B12","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1161\/ATVBAHA.109.185801","article-title":"Thrombin induces EGF receptor expression and cell proliferation via a PKC(delta)\/c-Src-dependent pathway in vascular smooth muscle cells","volume":"29","author":"Hsieh","year":"2009","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"2021113010393881800_B13","doi-asserted-by":"publisher","first-page":"1936","DOI":"10.1096\/fj.05-5328fje","article-title":"Heparin binding EGF is necessary for vasospastic response to endothelin","volume":"20","author":"Chansel","year":"2006","journal-title":"FASEB J."},{"key":"2021113010393881800_B14","doi-asserted-by":"publisher","first-page":"8740","DOI":"10.1074\/jbc.M310012200","article-title":"UTP transactivates epidermal growth factor receptors and promotes cardiomyocyte hypertrophy despite inhibiting transcription of the hypertrophic marker gene, atrial natriuretic peptide","volume":"279","author":"Morris","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2021113010393881800_B15","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1291\/hypres.30.979","article-title":"Aldosterone-and-salt-induced cardiac fibrosis is independent from angiotensin II type\u00a01a receptor signaling in mice","volume":"30","author":"Kagiyama","year":"2007","journal-title":"Hypertens. Res."},{"key":"2021113010393881800_B16","doi-asserted-by":"publisher","first-page":"7430","DOI":"10.1038\/srep07430","article-title":"Moderate inappropriately high aldosterone\/NaCl constellation in mice: cardiovascular effects and the role of cardiovascular epidermal growth factor receptor","volume":"4","author":"Schreier","year":"2014","journal-title":"Sci. Rep."},{"key":"2021113010393881800_B17","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1093\/cvr\/cvr308","article-title":"Nox1 transactivation of epidermal growth factor receptor promotes N-cadherin shedding and smooth muscle cell migration","volume":"93","author":"Jagadeesha","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"2021113010393881800_B18","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1242\/jcs.02772","article-title":"The beta 2-adrenergic receptor activates pro-migratory and pro-proliferative pathways in dermal fibroblasts via divergent mechanisms","volume":"119","author":"Pullar","year":"2006","journal-title":"J. Cell Sci."},{"key":"2021113010393881800_B19","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1161\/ATVBAHA.111.223537","article-title":"Consequences of epidermal growth factor receptor (ErbB1) loss for vascular smooth muscle cells from mice with targeted deletion of ErbB1","volume":"31","author":"Schreier","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"2021113010393881800_B20","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1590\/S0100-879X2000000600002","article-title":"Angiotensin II-mediated vascular smooth muscle cell growth signaling","volume":"33","author":"Inagami","year":"2000","journal-title":"Braz. J. Med. Biol. Res."},{"key":"2021113010393881800_B21","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1002\/jcp.20250","article-title":"Bradykinin-induced p42\/p44 MAPK phosphorylation and cell proliferation via Src, EGF receptors, and PI3-K\/Akt in vascular smooth muscle cells","volume":"203","author":"Yang","year":"2005","journal-title":"J. Cell. Physiol."},{"key":"2021113010393881800_B22","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/0165-6147(81)90359-X","article-title":"Age-related decrease in beta adrenoceptor activity of the cardiovascular system","volume":"2","author":"Fleisch","year":"1981","journal-title":"Trends Pharmacol. Sci."},{"key":"2021113010393881800_B23","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1089\/ars.2009.2857","article-title":"A differential role for endocytosis in receptor-mediated activation of Nox1","volume":"12","author":"Miller","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"2021113010393881800_B24","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1096\/fj.02-0115fje","article-title":"Epidermal growth factor receptor trans-activation mediates the tonic and fibrogenic effects of endothelin in the aortic wall of transgenic mice","volume":"17","author":"Flamant","year":"2003","journal-title":"FASEB J."},{"key":"2021113010393881800_B25","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1161\/HYPERTENSIONAHA.114.04794","article-title":"Epidermal growth factor receptor is critical for angiotensin II-mediated hypertrophy in cerebral arterioles","volume":"65","author":"Chan","year":"2015","journal-title":"Hypertension"},{"key":"2021113010393881800_B26","doi-asserted-by":"publisher","first-page":"S182","DOI":"10.1097\/00005344-199800001-00052","article-title":"Endothelin-1 stimulates DNA synthesis of vascular smooth-muscle cells through transactivation of epidermal growth factor receptor","volume":"31","author":"Iwasaki","year":"1998","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"2021113010393881800_B27","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1161\/HYPERTENSIONAHA.109.148783","article-title":"Elevated mineralocorticoid receptor activity in aged rat vascular smooth muscle cells promotes a proinflammatory phenotype via extracellular signal-regulated kinase 1\/2 mitogen-activated protein kinase and epidermal growth factor receptor-dependent pathways","volume":"55","author":"Krug","year":"2010","journal-title":"Hypertension"},{"key":"2021113010393881800_B28","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1038\/nm.2891","article-title":"Direct regulation of blood pressure by smooth muscle cell mineralocorticoid receptors","volume":"18","author":"McCurley","year":"2012","journal-title":"Nat. Med."},{"key":"2021113010393881800_B29","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1159\/000362548","article-title":"Proinflammation of aging central arteries: a mini-review","volume":"60","author":"Wang","year":"2014","journal-title":"Gerontology"},{"key":"2021113010393881800_B30","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1126\/science.7618085","article-title":"Strain-dependent epithelial defects in mice lacking the EGF receptor","volume":"269","author":"Sibilia","year":"1995","journal-title":"Science"},{"key":"2021113010393881800_B31","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1111\/j.1432-0436.2007.00238.x","article-title":"The epidermal growth factor receptor: from development to tumorigenesis","volume":"75","author":"Sibilia","year":"2007","journal-title":"Differentiation"},{"key":"2021113010393881800_B32","doi-asserted-by":"publisher","first-page":"17081","DOI":"10.1073\/pnas.0704126104","article-title":"The EGF receptor is required for efficient liver regeneration","volume":"104","author":"Natarajan","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113010393881800_B33","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/nm1666","article-title":"G12-G13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension","volume":"14","author":"Wirth","year":"2008","journal-title":"Nat. Med."},{"key":"2021113010393881800_B34","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1161\/CIRCULATIONAHA.109.890962","article-title":"Smooth muscle-specific deletion of nitric oxide-sensitive guanylyl cyclase is sufficient to induce hypertension in mice","volume":"121","author":"Groneberg","year":"2010","journal-title":"Circulation"},{"key":"2021113010393881800_B35","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s00441-003-0731-3","article-title":"Combined lack of estrogen receptors alpha and beta affects vascular iNOS protein expression","volume":"313","author":"Liang","year":"2003","journal-title":"Cell Tissue Res."},{"key":"2021113010393881800_B36","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1161\/01.RES.41.1.19","article-title":"Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats","volume":"41","author":"Mulvany","year":"1977","journal-title":"Circ. Res."},{"key":"2021113010393881800_B37","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1161\/01.CIR.74.5.1107","article-title":"The effect of vasoactive agents on the left ventricular end-systolic pressure-volume relation in closed-chest dogs","volume":"74","author":"Freeman","year":"1986","journal-title":"Circulation"},{"key":"2021113010393881800_B38","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.yexcr.2008.10.024","article-title":"Ligand-induced ErbB receptor dimerization","volume":"315","author":"Lemmon","year":"2009","journal-title":"Exp. Cell Res."},{"key":"2021113010393881800_B39","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1161\/01.HYP.0000035397.73223.CE","article-title":"Gq-Coupled receptor agonists mediate cardiac hypertrophy via the vasculature","volume":"40","author":"Keys","year":"2002","journal-title":"Hypertension"},{"key":"2021113010393881800_B40","doi-asserted-by":"publisher","first-page":"17132","DOI":"10.1073\/pnas.0406041101","article-title":"Restricted inactivation of serum response factor to the cardiovascular system","volume":"101","author":"Miano","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113010393881800_B41","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1111\/j.1476-5381.1996.tb15516.x","article-title":"Modification of aortic contractility in the cardiomyopathic hamster","volume":"118","author":"Dumont","year":"1996","journal-title":"Br. J. Pharmacol."},{"key":"2021113010393881800_B42","first-page":"10","article-title":"Vasorelaxant effect of a newly synthesized dihydropyridine ethyl ester (DHPEE) on rat thoracic aorta: dual mechanism of action","volume":"1","author":"Babaei","year":"2011","journal-title":"Adv. Pharm. Bull."},{"key":"2021113010393881800_B43","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1006\/bbrc.1994.1253","article-title":"Novel subtype of human angiotensin II type\u00a01 receptor: analysis of signal transduction mechanism in transfected Chinese hamster ovary cells","volume":"199","author":"Kuroda","year":"1994","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021113010393881800_B44","doi-asserted-by":"publisher","first-page":"H376","DOI":"10.1152\/ajpheart.00649.2014","article-title":"Caveolin-1 prevents sustained angiotensin II-induced resistance artery constriction and obesity-induced high blood pressure","volume":"308","author":"Czikora","year":"2015","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2021113010393881800_B45","doi-asserted-by":"publisher","first-page":"S20","DOI":"10.1097\/01.fjc.0000166220.65593.22","article-title":"EGF receptor transactivation in angiotensin II and endothelin control of vascular protein synthesis in\u00a0vivo","volume":"44","author":"Beaucage","year":"2004","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"2021113010393881800_B46","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1046\/j.1523-1755.2000.00201.x","article-title":"Angiotensin II-induced growth of vascular smooth muscle cells requires an Src-dependent activation of the epidermal growth factor receptor","volume":"58","author":"Bokemeyer","year":"2000","journal-title":"Kidney Int."},{"key":"2021113010393881800_B47","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1161\/01.ATV.0000134529.65173.08","article-title":"Rat aortic MCP-1 and its receptor CCR2 increase with age and alter vascular smooth muscle cell function","volume":"24","author":"Spinetti","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/130\/1\/19\/444103\/cs1300019.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/130\/1\/19\/444103\/cs1300019.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T11:30:11Z","timestamp":1638271811000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/130\/1\/19\/71297\/Consequences-of-postnatal-vascular-smooth-muscle"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,30]]},"references-count":47,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2016,1,1]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20150503","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,30]]}}}