{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:07:52Z","timestamp":1792706872724,"version":"4.5.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2017,3,7]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells in situ represents a promising strategy for cardiac regeneration. A combination of 3 cardiac transcription factors, Gata4, Mef2c, and Tbx5 (GMT), can convert fibroblasts into induced cardiomyocyte-like cells, albeit with low efficiency in vitro.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>We screened 5500 compounds in primary cardiac fibroblasts to identify the pathways that can be modulated to enhance cardiomyocyte reprogramming.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>We found that a combination of the transforming growth factor-\u03b2 inhibitor SB431542 and the WNT inhibitor XAV939 increased reprogramming efficiency 8-fold when added to GMT-overexpressing cardiac fibroblasts. The small molecules also enhanced the speed and quality of cell conversion; we observed beating cells as early as 1 week after reprogramming compared with 6 to 8 weeks with GMT alone. In vivo, mice exposed to GMT, SB431542, and XAV939 for 2 weeks after myocardial infarction showed significantly improved reprogramming and cardiac function compared with those exposed to only GMT. Human cardiac reprogramming was similarly enhanced on transforming growth factor-\u03b2 and WNT inhibition and was achieved most efficiently with GMT plus myocardin.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Transforming growth factor-\u03b2 and WNT inhibitors jointly enhance GMT-induced direct cardiac reprogramming from cardiac fibroblasts in vitro and in vivo and provide a more robust platform for cardiac regeneration.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.116.024692","type":"journal-article","created":{"date-parts":[[2016,11,14]],"date-time":"2016-11-14T11:06:32Z","timestamp":1479121592000},"page":"978-995","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":212,"title":["Chemical Enhancement of In Vitro and In Vivo Direct Cardiac Reprogramming"],"prefix":"10.1161","volume":"135","author":[{"given":"Tamer M. A.","family":"Mohamed","sequence":"first","affiliation":[{"name":"From Gladstone Institute of Cardiovascular Disease and Roddenberry Center for Stem Cell Biology and Medicine, San Francisco, CA (T.M.A.M., N.R.S., E.C.B., E.R., Y.H., K.P., Y.-S.A., P.Y., H.W., S.T., S.D., K.N.I., D.S.); Institute of Cardiovascular Sciences, University of Manchester, UK (T.M.A.M.); Faculty of Pharmacy, Zagazig University, Egypt (T.M.A.M.); and Departments of Radiology (S.M.), Pharmaceutical Chemistry (S.D.), Pediatrics (K.N.I., D.S.), and Biochemistry and Biophysics (D.S.),..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole R.","family":"Stone","sequence":"additional","affiliation":[{"name":"From Gladstone Institute of Cardiovascular Disease and Roddenberry Center for Stem Cell Biology and Medicine, San Francisco, CA (T.M.A.M., N.R.S., E.C.B., E.R., Y.H., K.P., Y.-S.A., P.Y., H.W., S.T., S.D., K.N.I., D.S.); Institute of Cardiovascular Sciences, University of Manchester, UK (T.M.A.M.); Faculty of Pharmacy, Zagazig University, Egypt (T.M.A.M.); and Departments of Radiology (S.M.), Pharmaceutical Chemistry (S.D.), Pediatrics (K.N.I., D.S.), and Biochemistry and Biophysics (D.S.),..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily C.","family":"Berry","sequence":"additional","affiliation":[{"name":"From Gladstone Institute of Cardiovascular Disease and Roddenberry Center for Stem Cell Biology and Medicine, San Francisco, CA (T.M.A.M., N.R.S., E.C.B., E.R., Y.H., K.P., Y.-S.A., P.Y., H.W., S.T., S.D., K.N.I., D.S.); Institute of Cardiovascular Sciences, University of Manchester, UK (T.M.A.M.); Faculty of Pharmacy, Zagazig University, Egypt (T.M.A.M.); and Departments of Radiology (S.M.), Pharmaceutical Chemistry (S.D.), Pediatrics (K.N.I., D.S.), and Biochemistry and Biophysics (D.S.),..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Radzinsky","sequence":"additional","affiliation":[{"name":"From Gladstone Institute of Cardiovascular Disease and Roddenberry Center for Stem Cell Biology and Medicine, San Francisco, CA (T.M.A.M., N.R.S., E.C.B., E.R., Y.H., K.P., Y.-S.A., P.Y., H.W., S.T., S.D., K.N.I., D.S.); Institute of Cardiovascular Sciences, University of Manchester, UK (T.M.A.M.); Faculty of Pharmacy, Zagazig University, Egypt (T.M.A.M.); and Departments of Radiology (S.M.), Pharmaceutical Chemistry (S.D.), Pediatrics (K.N.I., D.S.), and Biochemistry and Biophysics (D.S.),..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"From Gladstone Institute of Cardiovascular Disease and Roddenberry Center for Stem Cell Biology and Medicine, San Francisco, CA (T.M.A.M., N.R.S., E.C.B., E.R., Y.H., K.P., Y.-S.A., P.Y., H.W., S.T., S.D., K.N.I., D.S.); Institute of Cardiovascular Sciences, University of Manchester, UK (T.M.A.M.); Faculty of Pharmacy, Zagazig University, Egypt (T.M.A.M.); and Departments of Radiology (S.M.), Pharmaceutical Chemistry (S.D.), Pediatrics (K.N.I., D.S.), and Biochemistry and Biophysics (D.S.),..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karishma","family":"Pratt","sequence":"additional","affiliation":[{"name":"From Gladstone Institute of Cardiovascular Disease and Roddenberry Center for Stem Cell Biology and Medicine, San Francisco, CA (T.M.A.M., N.R.S., E.C.B., E.R., Y.H., K.P., Y.-S.A., P.Y., H.W., S.T., S.D., K.N.I., D.S.); Institute of Cardiovascular Sciences, University of Manchester, UK (T.M.A.M.); Faculty of Pharmacy, Zagazig University, Egypt (T.M.A.M.); and Departments of Radiology (S.M.), Pharmaceutical Chemistry (S.D.), Pediatrics (K.N.I., D.S.), and Biochemistry and Biophysics (D.S.),..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Sin","family":"Ang","sequence":"additional","affiliation":[{"name":"From Gladstone Institute of Cardiovascular Disease and Roddenberry Center for Stem Cell Biology and Medicine, San Francisco, CA (T.M.A.M., N.R.S., E.C.B., E.R., Y.H., K.P., Y.-S.A., P.Y., H.W., S.T., S.D., K.N.I., D.S.); Institute of Cardiovascular Sciences, University of Manchester, UK (T.M.A.M.); Faculty of Pharmacy, Zagazig University, Egypt (T.M.A.M.); and Departments of Radiology (S.M.), Pharmaceutical Chemistry (S.D.), Pediatrics (K.N.I., D.S.), and Biochemistry and Biophysics (D.S.),..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengzhi","family":"Yu","sequence":"additional","affiliation":[{"name":"From Gladstone Institute of Cardiovascular Disease and Roddenberry Center for Stem Cell Biology and Medicine, San Francisco, CA (T.M.A.M., N.R.S., E.C.B., E.R., Y.H., K.P., Y.-S.A., P.Y., H.W., S.T., S.D., K.N.I., D.S.); Institute of Cardiovascular Sciences, University of Manchester, UK (T.M.A.M.); Faculty of Pharmacy, Zagazig University, Egypt (T.M.A.M.); and Departments of Radiology (S.M.), Pharmaceutical Chemistry (S.D.), Pediatrics (K.N.I., D.S.), and Biochemistry and Biophysics (D.S.),..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixia","family":"Wang","sequence":"additional","affiliation":[{"name":"From Gladstone Institute of Cardiovascular Disease and Roddenberry Center for Stem Cell Biology and Medicine, San Francisco, CA (T.M.A.M., N.R.S., E.C.B., E.R., Y.H., K.P., Y.-S.A., P.Y., H.W., S.T., S.D., K.N.I., D.S.); Institute of Cardiovascular Sciences, University of Manchester, UK (T.M.A.M.); Faculty of Pharmacy, Zagazig University, Egypt (T.M.A.M.); and Departments of Radiology (S.M.), Pharmaceutical Chemistry (S.D.), Pediatrics (K.N.I., D.S.), and Biochemistry and Biophysics (D.S.),..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibing","family":"Tang","sequence":"additional","affiliation":[{"name":"From Gladstone Institute of Cardiovascular Disease and Roddenberry Center for Stem Cell Biology and Medicine, San Francisco, CA (T.M.A.M., N.R.S., E.C.B., E.R., Y.H., K.P., Y.-S.A., P.Y., H.W., S.T., S.D., K.N.I., D.S.); Institute of Cardiovascular Sciences, University of Manchester, UK (T.M.A.M.); Faculty of Pharmacy, Zagazig University, Egypt (T.M.A.M.); and Departments of Radiology (S.M.), Pharmaceutical Chemistry (S.D.), Pediatrics (K.N.I., D.S.), and Biochemistry and Biophysics (D.S.),..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Magnitsky","sequence":"additional","affiliation":[{"name":"From Gladstone Institute of Cardiovascular Disease and Roddenberry Center for Stem Cell Biology and Medicine, San Francisco, CA (T.M.A.M., N.R.S., E.C.B., E.R., Y.H., K.P., Y.-S.A., P.Y., H.W., S.T., S.D., K.N.I., D.S.); Institute of Cardiovascular Sciences, University of Manchester, UK (T.M.A.M.); Faculty of Pharmacy, Zagazig University, Egypt (T.M.A.M.); and Departments of Radiology (S.M.), Pharmaceutical Chemistry (S.D.), Pediatrics (K.N.I., D.S.), and Biochemistry and Biophysics (D.S.),..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Ding","sequence":"additional","affiliation":[{"name":"From Gladstone Institute of Cardiovascular Disease and Roddenberry Center for Stem Cell Biology and Medicine, San Francisco, CA (T.M.A.M., N.R.S., E.C.B., E.R., Y.H., K.P., Y.-S.A., P.Y., H.W., S.T., S.D., K.N.I., D.S.); Institute of Cardiovascular Sciences, University of Manchester, UK (T.M.A.M.); Faculty of Pharmacy, Zagazig University, Egypt (T.M.A.M.); and Departments of Radiology (S.M.), Pharmaceutical Chemistry (S.D.), Pediatrics (K.N.I., D.S.), and Biochemistry and Biophysics (D.S.),..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn N.","family":"Ivey","sequence":"additional","affiliation":[{"name":"From Gladstone Institute of Cardiovascular Disease and Roddenberry Center for Stem Cell Biology and Medicine, San Francisco, CA (T.M.A.M., N.R.S., E.C.B., E.R., Y.H., K.P., Y.-S.A., P.Y., H.W., S.T., S.D., K.N.I., D.S.); Institute of Cardiovascular Sciences, University of Manchester, UK (T.M.A.M.); Faculty of Pharmacy, Zagazig University, Egypt (T.M.A.M.); and Departments of Radiology (S.M.), Pharmaceutical Chemistry (S.D.), Pediatrics (K.N.I., D.S.), and Biochemistry and Biophysics (D.S.),..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Srivastava","sequence":"additional","affiliation":[{"name":"From Gladstone Institute of Cardiovascular Disease and Roddenberry Center for Stem Cell Biology and Medicine, San Francisco, CA (T.M.A.M., N.R.S., E.C.B., E.R., Y.H., K.P., Y.-S.A., P.Y., H.W., S.T., S.D., K.N.I., D.S.); Institute of Cardiovascular Sciences, University of Manchester, UK (T.M.A.M.); Faculty of Pharmacy, Zagazig University, Egypt (T.M.A.M.); and Departments of Radiology (S.M.), Pharmaceutical Chemistry (S.D.), Pediatrics (K.N.I., D.S.), and Biochemistry and Biophysics 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