| First Author | Molkentin JD | Year | 1998 |
| Journal | Cell | Volume | 93 |
| Issue | 2 | Pages | 215-28 |
| PubMed ID | 9568714 | Mgi Jnum | J:93176 |
| Mgi Id | MGI:3056159 | Doi | 10.1016/s0092-8674(00)81573-1 |
| Citation | Molkentin JD, et al. (1998) A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell 93(2):215-28 |
| abstractText | In response to numerous pathologic stimuli, the myocardium undergoes a hypertrophic response characterized by increased myocardial cell size and activation of fetal cardiac genes. We show that cardiac hypertrophy is induced by the calcium-dependent phosphatase calcineurin, which dephosphorylates the transcription factor NF-AT3, enabling it to translocate to the nucleus. NF-AT3 interacts with the cardiac zinc finger transcription factor GATA4, resulting in synergistic activation of cardiac transcription. Transgenic mice that express activated forms of calcineurin or NF-AT3 in the heart develop cardiac hypertrophy and heart failure that mimic human heart disease. Pharmacologic inhibition of calcineurin activity blocks hypertrophy in vivo and in vitro. These results define a novel hypertrophic signaling pathway and suggest pharmacologic approaches to prevent cardiac hypertrophy and heart failure. |
