{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:37:06Z","timestamp":1789425426791,"version":"build-2803163510"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2017,5,26]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>The pathogenesis of bicuspid aortic valve (BAV)\u2013associated aortopathy is poorly understood, and no prognostic biomarker is currently available.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>We aimed to identify putative circulating biomarkers pathogenetically and prognostically linked to bicuspid aortopathy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              By reverse transcription polymerase chain reaction, we evaluated gene expression variations (versus normal aorta) of transforming growth factor-\u03b21 (TGF-\u03b21), connective tissue growth factor, matrix metalloproteinase-2 (MMP-2), MMP-14, endoglin (ENG), and superoxide dismutase 3 in ascending aorta samples from 50 tricuspid and 70 patients with BAV undergoing surgery for aortic stenosis (aorta diameter \u226445 mm: BAV\n              <jats:sub>non-dil<\/jats:sub>\n              or &gt;45 mm: BAV\n              <jats:sub>dil<\/jats:sub>\n              ). Expression changes of the TGF-\u03b21 active dimer and ENG were analyzed also by Western blot in ascending aorta samples from other 10 tricuspid aortic valve, 10 BAV\n              <jats:sub>non-dil<\/jats:sub>\n              , and 10 BAV\n              <jats:sub>dil<\/jats:sub>\n              patients. The serum concentration of study targets was assessed through ELISA and the ratio of serum TGF-\u03b21\/ENG (T\/E) was evaluated. All BAV\n              <jats:sub>non-dil<\/jats:sub>\n              patients underwent follow-up echocardiography to assess aortic growth rate. In BAV\n              <jats:sub>non-dil<\/jats:sub>\n              patients, TGF-\u03b21 and MMP-2 gene expression increased significantly, whereas MMP-14 and ENG expression decreased versus controls. Expression changes were confirmed at protein level for TGF-\u03b21 and ENG. TGF-\u03b21 serum concentration significantly decreased in tricuspid aortic valve and BAV\n              <jats:sub>non-dil<\/jats:sub>\n              patients versus healthy subjects. ENG serum concentration decreased in all patients, more markedly in BAV\n              <jats:sub>dil<\/jats:sub>\n              . A significant increase of the T\/E ratio versus healthy subjects was unique of patients with BAV. In BAV\n              <jats:sub>non-dil<\/jats:sub>\n              patients, a T\/E \u22659 was independently associated in multivariable analysis with higher MMP-2 and lower superoxide dismutase 3 gene expression, independent of age and aortic diameter. A significant correlation was observed between baseline T\/E ratio and aortic diameter growth rate in BAV\n              <jats:sub>non-dil<\/jats:sub>\n              patients (\n              <jats:italic>r<\/jats:italic>\n              =0.66,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>The novel evidence of a possible value of the T\/E ratio as a biomarker of BAV aortopathy was presented: further validation studies are warranted.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.117.310833","type":"journal-article","created":{"date-parts":[[2017,4,19]],"date-time":"2017-04-19T00:50:28Z","timestamp":1492563028000},"page":"1800-1811","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":44,"title":["A Possible Early Biomarker for Bicuspid Aortopathy"],"prefix":"10.1161","volume":"120","author":[{"given":"Amalia","family":"Forte","sequence":"first","affiliation":[{"name":"From the Experimental Medicine (A.F., M.C.), Cardiothoracic Sciences (C.B., M.B., M.D.F., A.D.C.), and Biophysics, Biochemistry, and General Pathology (G.C.), University of Campania \u201cL.Vanvitelli\u201d, Naples Italy; and Department of Cardiac Surgery, Cardiovascular Center, Paracelsus Medical University, N\u00fcrnberg, Germany (G.S., T.J.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciro","family":"Bancone","sequence":"additional","affiliation":[{"name":"From the Experimental Medicine (A.F., M.C.), Cardiothoracic Sciences (C.B., M.B., M.D.F., A.D.C.), and Biophysics, Biochemistry, and General Pathology (G.C.), University of Campania \u201cL.Vanvitelli\u201d, Naples Italy; and Department of Cardiac Surgery, Cardiovascular Center, Paracelsus Medical University, N\u00fcrnberg, Germany (G.S., T.J.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilda","family":"Cobellis","sequence":"additional","affiliation":[{"name":"From the Experimental Medicine (A.F., M.C.), Cardiothoracic Sciences (C.B., M.B., M.D.F., A.D.C.), and Biophysics, Biochemistry, and General Pathology (G.C.), University of Campania \u201cL.Vanvitelli\u201d, Naples Italy; and Department of Cardiac Surgery, Cardiovascular Center, Paracelsus Medical University, N\u00fcrnberg, Germany (G.S., T.J.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Buonocore","sequence":"additional","affiliation":[{"name":"From the Experimental Medicine (A.F., M.C.), Cardiothoracic Sciences (C.B., M.B., M.D.F., A.D.C.), and Biophysics, Biochemistry, and General Pathology (G.C.), University of Campania \u201cL.Vanvitelli\u201d, Naples Italy; and Department of Cardiac Surgery, Cardiovascular Center, Paracelsus Medical University, N\u00fcrnberg, Germany (G.S., T.J.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Santarpino","sequence":"additional","affiliation":[{"name":"From the Experimental Medicine (A.F., M.C.), Cardiothoracic Sciences (C.B., M.B., M.D.F., A.D.C.), and Biophysics, Biochemistry, and General Pathology (G.C.), University of Campania \u201cL.Vanvitelli\u201d, Naples Italy; and Department of Cardiac Surgery, Cardiovascular Center, Paracelsus Medical University, N\u00fcrnberg, Germany (G.S., T.J.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodor J.M.","family":"Fischlein","sequence":"additional","affiliation":[{"name":"From the Experimental Medicine (A.F., M.C.), Cardiothoracic Sciences (C.B., M.B., M.D.F., A.D.C.), and Biophysics, Biochemistry, and General Pathology (G.C.), University of Campania \u201cL.Vanvitelli\u201d, Naples Italy; and Department of Cardiac Surgery, Cardiovascular Center, Paracelsus Medical University, N\u00fcrnberg, Germany (G.S., T.J.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Cipollaro","sequence":"additional","affiliation":[{"name":"From the Experimental Medicine (A.F., M.C.), Cardiothoracic Sciences (C.B., M.B., M.D.F., A.D.C.), and Biophysics, Biochemistry, and General Pathology (G.C.), University of Campania \u201cL.Vanvitelli\u201d, Naples Italy; and Department of Cardiac Surgery, Cardiovascular Center, Paracelsus Medical University, N\u00fcrnberg, Germany (G.S., T.J.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"De Feo","sequence":"additional","affiliation":[{"name":"From the Experimental Medicine (A.F., M.C.), Cardiothoracic Sciences (C.B., M.B., M.D.F., A.D.C.), and Biophysics, Biochemistry, and General Pathology (G.C.), University of Campania \u201cL.Vanvitelli\u201d, Naples Italy; and Department of Cardiac Surgery, Cardiovascular Center, Paracelsus Medical University, N\u00fcrnberg, Germany (G.S., T.J.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Della Corte","sequence":"additional","affiliation":[{"name":"From the Experimental Medicine (A.F., M.C.), Cardiothoracic Sciences (C.B., M.B., M.D.F., A.D.C.), and Biophysics, Biochemistry, and General Pathology (G.C.), University of Campania \u201cL.Vanvitelli\u201d, Naples Italy; and Department of Cardiac Surgery, Cardiovascular Center, Paracelsus Medical University, N\u00fcrnberg, Germany (G.S., 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