{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:44:30Z","timestamp":1791398670017,"version":"4.3.3"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2010,5,28]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Rationale<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            Numerous studies have proposed that glycogen synthase kinase (GSK)-3\u03b2 is a central regulator of the hypertrophic response of cardiomyocytes. However, all of this work has relied on overexpression of GSK-3\u03b2, expression of constitutively active mutants, or small molecule inhibitors with documented off-target effects. Genetic loss of function approaches have not been used in the adult mouse because germ-line deletion of GSK-3\u03b2 is embryonic-lethal.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Objective<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            This study was designed to define the role played by GSK-3\u03b2 in pressure overload (PO)-induced hypertrophy and remodeling following myocardial infarction (MI).\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Methods and Results<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            We used a mouse model that allows inducible, cardiomyocyte-specific deletion of GSK-3\u03b2 in the adult knockout. Surprisingly, we find that knockout mice exposed to PO induced by thoracic aortic constriction exhibit a normal hypertrophic response. Thus, in contrast to virtually all prior published studies, GSK-3\u03b2 appears to play at most a minor role in the hypertrophic response to PO stress. However, GSK-3\u03b2 does regulate post-MI remodeling because the GSK-3\u03b2 knockouts had less left ventricular dilatation and better-preserved left ventricular function at up to 8 weeks post-MI despite demonstrating significantly more hypertrophy in the remote myocardium. Deletion of GSK-3\u03b2 also led to increased cardiomyocyte proliferation following PO and MI.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Conclusions<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            Deletion of GSK-3\u03b2 protects against post-MI remodeling and promotes stress-induced cardiomyocyte proliferation in the adult heart. These studies suggest that inhibition of GSK-3\u03b2 could be a strategy to both prevent remodeling and to promote cardiac regeneration in pathological states.\n          <\/jats:p>","DOI":"10.1161\/circresaha.109.211482","type":"journal-article","created":{"date-parts":[[2010,4,2]],"date-time":"2010-04-02T00:59:04Z","timestamp":1270169944000},"page":"1635-1645","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":114,"title":["Glycogen Synthase Kinase-3\u03b2 Regulates Post\u2013Myocardial Infarction Remodeling and Stress-Induced Cardiomyocyte Proliferation In Vivo"],"prefix":"10.1161","volume":"106","author":[{"given":"Kathleen C.","family":"Woulfe","sequence":"first","affiliation":[{"name":"From the Center for Translational Medicine and Cardiology Division (K.C.W., E.G., H.L., D.H., Q.F., R.V., M.D., X.S., T.F., J.Z.), Thomas Jefferson University, Philadelphia, Pa; and Samuel Lunenfeld Research Institute (S.P., J.R.W.), Mount Sinai Hospital, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erhe","family":"Gao","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine and Cardiology Division (K.C.W., E.G., H.L., D.H., Q.F., R.V., M.D., X.S., T.F., J.Z.), Thomas Jefferson University, Philadelphia, Pa; and Samuel Lunenfeld Research Institute (S.P., J.R.W.), Mount Sinai Hospital, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hind","family":"Lal","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine and Cardiology Division (K.C.W., E.G., H.L., D.H., Q.F., R.V., M.D., X.S., T.F., J.Z.), Thomas Jefferson University, Philadelphia, Pa; and Samuel Lunenfeld Research Institute (S.P., J.R.W.), Mount Sinai Hospital, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Harris","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine and Cardiology Division (K.C.W., E.G., H.L., D.H., Q.F., R.V., M.D., X.S., T.F., J.Z.), Thomas Jefferson University, Philadelphia, Pa; and Samuel Lunenfeld Research Institute (S.P., J.R.W.), Mount Sinai Hospital, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Fan","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine and Cardiology Division (K.C.W., E.G., H.L., D.H., Q.F., R.V., M.D., X.S., T.F., J.Z.), Thomas Jefferson University, Philadelphia, Pa; and Samuel Lunenfeld Research Institute (S.P., J.R.W.), Mount Sinai Hospital, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Vagnozzi","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine and Cardiology Division (K.C.W., E.G., H.L., D.H., Q.F., R.V., M.D., X.S., T.F., J.Z.), Thomas Jefferson University, Philadelphia, Pa; and Samuel Lunenfeld Research Institute (S.P., J.R.W.), Mount Sinai Hospital, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan","family":"DeCaul","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine and Cardiology Division (K.C.W., E.G., H.L., D.H., Q.F., R.V., M.D., X.S., T.F., J.Z.), Thomas Jefferson University, Philadelphia, Pa; and Samuel Lunenfeld Research Institute (S.P., J.R.W.), Mount Sinai Hospital, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiying","family":"Shang","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine and Cardiology Division (K.C.W., E.G., H.L., D.H., Q.F., R.V., M.D., X.S., T.F., J.Z.), Thomas Jefferson University, Philadelphia, Pa; and Samuel Lunenfeld Research Institute (S.P., J.R.W.), Mount Sinai Hospital, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satish","family":"Patel","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine and Cardiology Division (K.C.W., E.G., H.L., D.H., Q.F., R.V., M.D., X.S., T.F., J.Z.), Thomas Jefferson University, Philadelphia, Pa; and Samuel Lunenfeld Research Institute (S.P., J.R.W.), Mount Sinai Hospital, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Woodgett","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine and Cardiology Division (K.C.W., E.G., H.L., D.H., Q.F., R.V., M.D., X.S., T.F., J.Z.), Thomas Jefferson University, Philadelphia, Pa; and Samuel Lunenfeld Research Institute (S.P., J.R.W.), Mount Sinai Hospital, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Force","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine and Cardiology Division (K.C.W., E.G., H.L., D.H., Q.F., R.V., M.D., X.S., T.F., J.Z.), Thomas Jefferson University, Philadelphia, Pa; 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