{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T13:50:25Z","timestamp":1793109025676,"version":"4.5.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2011,7,8]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Overexpression of muscle atrophy F-box (MAFbx\/atrogin-1), an E3 ubiquitin ligase, induces proteasomal degradation in cardiomyocytes. The role of endogenous MAFbx in regulating cardiac hypertrophy and failure remains unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>We investigated the role of MAFbx in regulating cardiac hypertrophy and function in response to pressure overload. Transverse aortic constriction (TAC) was applied to MAFbx knockout (KO) and wild-type (WT) mice.<\/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>Expression of MAFbx in WT mice was significantly increased by TAC. TAC-induced increases in cardiac hypertrophy were significantly smaller in MAFbx KO than in WT mice. There was significantly less lung congestion and interstitial fibrosis in MAFbx KO than in WT mice. MAFbx KO also inhibited \u03b2-adrenergic cardiac hypertrophy. DNA microarray analysis revealed that activation of genes associated with the transcription factor binding site for the nuclear factor-\u03baB family were inhibited in MAFbx KO mice compared with WT mice after TAC. Although the levels of I\u03baB-\u03b1 were significantly decreased after TAC in WT mice, they were increased in MAFbx KO mice. MAFbx regulates ubiquitination and proteasomal degradation of I\u03baB-\u03b1 in cardiomyocytes. In primary cultured rat cardiomyocytes, phenylephrine-induced activation of nuclear factor-\u03baB and hypertrophy were significantly suppressed by MAFbx knockdown but were partially rescued by overexpression of nuclear factor-\u03baB p65.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>MAFbx plays an essential role in mediating cardiac hypertrophy in response to pressure overload. Downregulation of MAFbx inhibits cardiac hypertrophy in part through stabilization of I\u03baB-\u03b1 and inactivation of nuclear factor-\u03baB. Taken together, inhibition of MAFbx attenuates pathological hypertrophy, thereby protecting the heart from progression into heart failure.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.110.238717","type":"journal-article","created":{"date-parts":[[2011,5,27]],"date-time":"2011-05-27T04:00:45Z","timestamp":1306468845000},"page":"161-171","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":73,"title":["Endogenous Muscle Atrophy F-Box Mediates Pressure Overload\u2013Induced Cardiac Hypertrophy Through Regulation of Nuclear Factor-\u03baB"],"prefix":"10.1161","volume":"109","author":[{"given":"Soichiro","family":"Usui","sequence":"first","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, Newark, NJ (S.U., Y.M., C.H., J.C., D.Z., J.S.); the Department of Biochemistry and Molecular Biology, UMDNJ, New Jersey Medical School, Newark, NJ (J.Y.Y., B.T.); Novartis Institutes for Biomedical Research, Cambridge, MA (D.J.G.); and the Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan (S.U.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Maejima","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, Newark, NJ (S.U., Y.M., C.H., J.C., D.Z., J.S.); the Department of Biochemistry and Molecular Biology, UMDNJ, New Jersey Medical School, Newark, NJ (J.Y.Y., B.T.); Novartis Institutes for Biomedical Research, Cambridge, MA (D.J.G.); and the Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan (S.U.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayashree","family":"Pain","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, Newark, NJ (S.U., Y.M., C.H., J.C., D.Z., J.S.); the Department of Biochemistry and Molecular Biology, UMDNJ, New Jersey Medical School, Newark, NJ (J.Y.Y., B.T.); Novartis Institutes for Biomedical Research, Cambridge, MA (D.J.G.); and the Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan (S.U.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chull","family":"Hong","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, Newark, NJ (S.U., Y.M., C.H., J.C., D.Z., J.S.); the Department of Biochemistry and Molecular Biology, UMDNJ, New Jersey Medical School, Newark, NJ (J.Y.Y., B.T.); Novartis Institutes for Biomedical Research, Cambridge, MA (D.J.G.); and the Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan (S.U.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeyeaon","family":"Cho","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, Newark, NJ (S.U., Y.M., C.H., J.C., D.Z., J.S.); the Department of Biochemistry and Molecular Biology, UMDNJ, New Jersey Medical School, Newark, NJ (J.Y.Y., B.T.); Novartis Institutes for Biomedical Research, Cambridge, MA (D.J.G.); and the Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan (S.U.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Yeon","family":"Park","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, Newark, NJ (S.U., Y.M., C.H., J.C., D.Z., J.S.); the Department of Biochemistry and Molecular Biology, UMDNJ, New Jersey Medical School, Newark, NJ (J.Y.Y., B.T.); Novartis Institutes for Biomedical Research, Cambridge, MA (D.J.G.); and the Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan (S.U.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Zablocki","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, Newark, NJ (S.U., Y.M., C.H., J.C., D.Z., J.S.); the Department of Biochemistry and Molecular Biology, UMDNJ, New Jersey Medical School, Newark, NJ (J.Y.Y., B.T.); Novartis Institutes for Biomedical Research, Cambridge, MA (D.J.G.); and the Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan (S.U.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Tian","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, Newark, NJ (S.U., Y.M., C.H., J.C., D.Z., J.S.); the Department of Biochemistry and Molecular Biology, UMDNJ, New Jersey Medical School, Newark, NJ (J.Y.Y., B.T.); Novartis Institutes for Biomedical Research, Cambridge, MA (D.J.G.); and the Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan (S.U.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Glass","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, Newark, NJ (S.U., Y.M., C.H., J.C., D.Z., J.S.); the Department of Biochemistry and Molecular Biology, UMDNJ, New Jersey Medical School, Newark, NJ (J.Y.Y., B.T.); Novartis Institutes for Biomedical Research, Cambridge, MA (D.J.G.); and the Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan (S.U.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Sadoshima","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, UMDNJ, New Jersey Medical School, Newark, NJ (S.U., Y.M., C.H., J.C., D.Z., J.S.); the Department of Biochemistry and Molecular Biology, UMDNJ, New Jersey Medical School, Newark, NJ (J.Y.Y., B.T.); Novartis Institutes for Biomedical Research, Cambridge, MA (D.J.G.); and the 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