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The only effective treatment is surgery, and this comes with complications and no guarantee of long-term success.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>Outcomes from pharmacological initiatives remain unsubstantiated and, therefore, the aim of this study is to determine if repurposing a selective XPO1 (exportin-1) inhibitor drug (KPT-330) is beneficial in the treatment of CAVD.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results:<\/jats:title>\n            <jats:p>\n              We show that KPT-330 prevents, attenuates, and mitigates calcific nodule formation in heart valve interstitial cells in vitro and prevents CAVD in\n              <jats:italic>Klotho<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice. Using RNA-sequencing and mass spectrometry, we show that KPT-330\u2019s beneficial effect is mediated by inhibiting nuclear export of the C\/EBP\u03b2 (transcription factor CCAAT\/enhancing-binding protein) in valve interstitial cells, leading to repression of canonical Wnt signaling, in part, through activation of the Wnt antagonist\n              <jats:italic>Axin1<\/jats:italic>\n              , and a subsequent decrease in proosteogenic markers and cell viability.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Our findings have met a critical need to discover alternative, pharmacological-based therapies in the treatment of CAVD.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.120.318503","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T11:25:08Z","timestamp":1613733908000},"page":"1300-1316","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["KPT-330 Prevents Aortic Valve Calcification via a Novel C\/EBP\u03b2 Signaling Pathway"],"prefix":"10.1161","volume":"128","author":[{"given":"Punashi","family":"Dutta","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Medical College of Wisconsin, Milwaukee (P.D., K.M.K., K.T., J.L.)."},{"name":"Pediatric Cardiology, The Herma Heart Institute, Children\u2019s Wisconsin, Milwaukee (P.D., K.M.K., K.T., J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik M.","family":"Kodigepalli","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical College of Wisconsin, Milwaukee (P.D., K.M.K., K.T., J.L.)."},{"name":"Pediatric Cardiology, The Herma Heart Institute, Children\u2019s Wisconsin, Milwaukee (P.D., K.M.K., K.T., J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"LaHaye","sequence":"additional","affiliation":[{"name":"The Institute for Genomic Medicine at Nationwide Children\u2019s Hospital, Columbus, OH (S.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Will","family":"Thompson","sequence":"additional","affiliation":[{"name":"Pharmacology and Cancer Biology, Duke University, Durham, NC (J.W.T., S.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Rains","sequence":"additional","affiliation":[{"name":"Pharmacology and Cancer Biology, Duke University, Durham, NC (J.W.T., S.R.)."},{"name":"Duke Proteomics and Metabolomics Shared Resource, Durham, NC (S.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey","family":"Nagel","sequence":"additional","affiliation":[{"name":"Ocean Ridge Biosciences, Deerfield Beach, FL (C.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn","family":"Thatcher","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical College of Wisconsin, Milwaukee (P.D., K.M.K., K.T., J.L.)."},{"name":"Pediatric Cardiology, The Herma Heart Institute, Children\u2019s Wisconsin, Milwaukee (P.D., K.M.K., K.T., J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Hinton","sequence":"additional","affiliation":[{"name":"Division of Molecular Cardiovascular Biology, Cincinnati Children\u2019s Hospital Medical Center, OH (R.B.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1517-6888","authenticated-orcid":true,"given":"Joy","family":"Lincoln","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical College of Wisconsin, Milwaukee (P.D., K.M.K., K.T., J.L.)."},{"name":"Pediatric Cardiology, The Herma Heart Institute, Children\u2019s Wisconsin, Milwaukee (P.D., K.M.K., K.T., J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0b013e31823ac046"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2008.04.056"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9149(01)01821-5"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.07.072"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/hc4301.098249"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000140723.15274.53"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08161-8"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0735-1097(02)02496-8"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.900027"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2008.04.060"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043876"},{"key":"e_1_3_6_13_2","first-page":"378","article-title":"Effect of statin treatment on aortic valve and coronary artery calcification.","volume":"16","author":"Mohler ER","year":"2007","unstructured":"Mohler, ER, 3rd, Wang, H, Medenilla, E, Scott, C. 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