{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T22:51:50Z","timestamp":1787698310445,"version":"build-2784847793"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>\n              EMILIN-1 (elastin microfibrils interface located protein-1) protein inhibits pro\u2013TGF-\u03b2 (transforming growth factor-\u03b2) proteolysis and limits TGF-\u03b2 bioavailability in vascular extracellular matrix.\n              <jats:italic>Emilin1<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              null mice display increased vascular TGF-\u03b2 signaling and are hypertensive. Because EMILIN-1 is expressed in vessels from embryonic life to adulthood, we aimed at unravelling whether the hypertensive phenotype of\n              <jats:italic>Emilin1<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              null mice results from a developmental defect or lack of homeostatic role in the adult.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>By using a conditional gene targeting inactivating EMILIN-1 in smooth muscle cells of adult mice, we show that increased blood pressure in mice with selective smooth muscle cell ablation of EMILIN-1 depends on enhanced myogenic tone. Mechanistically, we unveil that higher TGF-\u03b2 signaling in smooth muscle cells stimulates HB-EGF (heparin-binding epidermal growth factor) expression and subsequent transactivation of EGFR (epidermal growth factor receptor). With increasing intraluminal pressure in resistance arteries, the cross talk established by TGF-\u03b2 and EGFR signals recruits TRPC6 (TRP [transient receptor potential] classical type 6) and TRPM4 (TRP melastatin type 4) channels, lastly stimulating voltage-dependent calcium channels and potentiating myogenic tone. We found reduced EMILIN-1 and enhanced myogenic tone, dependent on increased TGF-\u03b2-EGFR signaling, in resistance arteries from hypertensive patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Taken together, our findings implicate an unexpected role of the TGF-\u03b2-EGFR pathway in hypertension with current translational perspectives.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.118.311115","type":"journal-article","created":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T13:52:45Z","timestamp":1538056365000},"page":"2484-2497","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Loss of EMILIN-1 Enhances Arteriolar Myogenic Tone Through TGF-\u03b2 (Transforming Growth Factor-\u03b2)\u2013Dependent Transactivation of EGFR (Epidermal Growth Factor Receptor) and Is Relevant for Hypertension in Mice and Humans"],"prefix":"10.1161","volume":"38","author":[{"given":"Daniela","family":"Carnevale","sequence":"first","affiliation":[{"name":"From the Department of Molecular Medicine, Sapienza University of Rome, Italy (D.C., M.P., G.L.)"},{"name":"Department of Angiocardioneurology and Translational Medicine (D.C., D.I., F.P., L.C., G.C., M.C., S.F., G.L.), IRCCS Neuromed, Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Facchinello","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine (N.F., D.B., F.D.R., P. 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