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Histone Methyltransferase SET1 Mediates Angiotensin II-Induced Endothelin-1 Transcription and Cardiac Hypertrophy in Mice.
Yu, Liming; Yang, Guang; Weng, Xinyu; Liang, Peng; Li, Luyang; Li, Jianfei; Fan, Zhiwen; Tian, Wenfang; Wu, Xiaoyan; Xu, Huihui; Fang, Minming; Ji, Yong; Li, Yuehua; Chen, Qi; Xu, Yong.
Afiliação
  • Yu L; From the Key Laboratory of Cardiovascular Disease and Department of Pathophysiology (L.Y., G.Y., X.W., P.L., L.L., J.L., Z.F., W.T., X.W., H.X., M.F., Y.J., Y.L., Q.C., Y.X.) and Laboratory Center for Basic Medical Sciences (X.W.), Nanjing Medical University, Nanjing, China; and Department of Surger
  • Yang G; From the Key Laboratory of Cardiovascular Disease and Department of Pathophysiology (L.Y., G.Y., X.W., P.L., L.L., J.L., Z.F., W.T., X.W., H.X., M.F., Y.J., Y.L., Q.C., Y.X.) and Laboratory Center for Basic Medical Sciences (X.W.), Nanjing Medical University, Nanjing, China; and Department of Surger
  • Weng X; From the Key Laboratory of Cardiovascular Disease and Department of Pathophysiology (L.Y., G.Y., X.W., P.L., L.L., J.L., Z.F., W.T., X.W., H.X., M.F., Y.J., Y.L., Q.C., Y.X.) and Laboratory Center for Basic Medical Sciences (X.W.), Nanjing Medical University, Nanjing, China; and Department of Surger
  • Liang P; From the Key Laboratory of Cardiovascular Disease and Department of Pathophysiology (L.Y., G.Y., X.W., P.L., L.L., J.L., Z.F., W.T., X.W., H.X., M.F., Y.J., Y.L., Q.C., Y.X.) and Laboratory Center for Basic Medical Sciences (X.W.), Nanjing Medical University, Nanjing, China; and Department of Surger
  • Li L; From the Key Laboratory of Cardiovascular Disease and Department of Pathophysiology (L.Y., G.Y., X.W., P.L., L.L., J.L., Z.F., W.T., X.W., H.X., M.F., Y.J., Y.L., Q.C., Y.X.) and Laboratory Center for Basic Medical Sciences (X.W.), Nanjing Medical University, Nanjing, China; and Department of Surger
  • Li J; From the Key Laboratory of Cardiovascular Disease and Department of Pathophysiology (L.Y., G.Y., X.W., P.L., L.L., J.L., Z.F., W.T., X.W., H.X., M.F., Y.J., Y.L., Q.C., Y.X.) and Laboratory Center for Basic Medical Sciences (X.W.), Nanjing Medical University, Nanjing, China; and Department of Surger
  • Fan Z; From the Key Laboratory of Cardiovascular Disease and Department of Pathophysiology (L.Y., G.Y., X.W., P.L., L.L., J.L., Z.F., W.T., X.W., H.X., M.F., Y.J., Y.L., Q.C., Y.X.) and Laboratory Center for Basic Medical Sciences (X.W.), Nanjing Medical University, Nanjing, China; and Department of Surger
  • Tian W; From the Key Laboratory of Cardiovascular Disease and Department of Pathophysiology (L.Y., G.Y., X.W., P.L., L.L., J.L., Z.F., W.T., X.W., H.X., M.F., Y.J., Y.L., Q.C., Y.X.) and Laboratory Center for Basic Medical Sciences (X.W.), Nanjing Medical University, Nanjing, China; and Department of Surger
  • Wu X; From the Key Laboratory of Cardiovascular Disease and Department of Pathophysiology (L.Y., G.Y., X.W., P.L., L.L., J.L., Z.F., W.T., X.W., H.X., M.F., Y.J., Y.L., Q.C., Y.X.) and Laboratory Center for Basic Medical Sciences (X.W.), Nanjing Medical University, Nanjing, China; and Department of Surger
  • Xu H; From the Key Laboratory of Cardiovascular Disease and Department of Pathophysiology (L.Y., G.Y., X.W., P.L., L.L., J.L., Z.F., W.T., X.W., H.X., M.F., Y.J., Y.L., Q.C., Y.X.) and Laboratory Center for Basic Medical Sciences (X.W.), Nanjing Medical University, Nanjing, China; and Department of Surger
  • Fang M; From the Key Laboratory of Cardiovascular Disease and Department of Pathophysiology (L.Y., G.Y., X.W., P.L., L.L., J.L., Z.F., W.T., X.W., H.X., M.F., Y.J., Y.L., Q.C., Y.X.) and Laboratory Center for Basic Medical Sciences (X.W.), Nanjing Medical University, Nanjing, China; and Department of Surger
  • Ji Y; From the Key Laboratory of Cardiovascular Disease and Department of Pathophysiology (L.Y., G.Y., X.W., P.L., L.L., J.L., Z.F., W.T., X.W., H.X., M.F., Y.J., Y.L., Q.C., Y.X.) and Laboratory Center for Basic Medical Sciences (X.W.), Nanjing Medical University, Nanjing, China; and Department of Surger
  • Li Y; From the Key Laboratory of Cardiovascular Disease and Department of Pathophysiology (L.Y., G.Y., X.W., P.L., L.L., J.L., Z.F., W.T., X.W., H.X., M.F., Y.J., Y.L., Q.C., Y.X.) and Laboratory Center for Basic Medical Sciences (X.W.), Nanjing Medical University, Nanjing, China; and Department of Surger
  • Chen Q; From the Key Laboratory of Cardiovascular Disease and Department of Pathophysiology (L.Y., G.Y., X.W., P.L., L.L., J.L., Z.F., W.T., X.W., H.X., M.F., Y.J., Y.L., Q.C., Y.X.) and Laboratory Center for Basic Medical Sciences (X.W.), Nanjing Medical University, Nanjing, China; and Department of Surger
  • Xu Y; From the Key Laboratory of Cardiovascular Disease and Department of Pathophysiology (L.Y., G.Y., X.W., P.L., L.L., J.L., Z.F., W.T., X.W., H.X., M.F., Y.J., Y.L., Q.C., Y.X.) and Laboratory Center for Basic Medical Sciences (X.W.), Nanjing Medical University, Nanjing, China; and Department of Surger
Arterioscler Thromb Vasc Biol ; 35(5): 1207-17, 2015 May.
Article em En | MEDLINE | ID: mdl-25814673
OBJECTIVE: Endothelin-1 is a potent vasoconstrictor derived from vascular endothelium. Elevated endothelin-1 levels are observed in a host of cardiovascular pathologies including cardiomyopathy. The epigenetic mechanism responsible for endothelin-1 induction in these pathological processes remains elusive. APPROACH AND RESULTS: We report here that induction of endothelin-1 expression in endothelial cells by angiotensin II (Ang II) was accompanied by the accumulation of histone H3K4 trimethylation, a preeminent histone modification for transcriptional activation, on the endothelin-1 promoter. In the meantime, Ang II stimulated the expression and the occupancy of Suv, Ez, and Trithorax domain 1 (SET1), a mammalian histone H3K4 trimethyltransferase, on the endothelin-1 promoter, both in vitro and in vivo. SET1 was recruited to the endothelin-1 promoter by activating protein 1 (c-Jun/c-Fos) and synergized with activating protein 1 to activate endothelin-1 transcription in response to Ang II treatment. Knockdown of SET1 in endothelial cells blocked Ang II-induced endothelin-1 synthesis and abrogated hypertrophy of cultured cardiomyocyte. Finally, endothelial-specific depletion of SET1 in mice attenuated Ang II-induced pathological hypertrophy and cardiac fibrosis. CONCLUSIONS: Our data suggest that SET1 epigenetically activates endothelin-1 transcription in endothelial cells, thereby contributing to Ang II-induced cardiac hypertrophy. As such, screening of small-molecule compound that inhibits SET1 activity will likely offer a new therapeutic solution to the treatment of cardiomyopathy.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Angiotensina II / Histona-Lisina N-Metiltransferase / Cardiomegalia / Endotelina-1 Limite: Animals Idioma: En Revista: Arterioscler Thromb Vasc Biol Assunto da revista: ANGIOLOGIA Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Angiotensina II / Histona-Lisina N-Metiltransferase / Cardiomegalia / Endotelina-1 Limite: Animals Idioma: En Revista: Arterioscler Thromb Vasc Biol Assunto da revista: ANGIOLOGIA Ano de publicação: 2015 Tipo de documento: Article