| First Author | Haubner BJ | Year | 2015 |
| Journal | Cardiovasc Res | Volume | 106 |
| Issue | 3 | Pages | 398-407 |
| PubMed ID | 25852081 | Mgi Jnum | J:250639 |
| Mgi Id | MGI:6106105 | Doi | 10.1093/cvr/cvv125 |
| Citation | Haubner BJ, et al. (2015) In vivo cardiac role of migfilin during experimental pressure overload. Cardiovasc Res 106(3):398-407 |
| abstractText | AIMS: Increased myocardial wall strain triggers the cardiac hypertrophic response by increasing cardiomyocyte size, reprogramming gene expression, and enhancing contractile protein synthesis. The LIM protein, migfilin, is a cytoskeleton-associated protein that was found to translocate in vitro into the nucleus in a Ca(2+)-dependent manner, where it co-activates the pivotal cardiac transcription factor Csx/Nkx2.5. However, the in vivo role of migfilin in cardiac function and stress response is unclear. METHODS AND RESULTS: To define the role of migfilin in cardiac hypertrophy, we induced hypertension by transverse aortic constriction (TAC) and compared cardiac morphology and function of migfilin knockout (KO) with wild-type (WT) hearts. Heart size and myocardial contractility were comparable in untreated migfilin KO and WT hearts, but migfilin-null hearts presented a reduced extent of hypertrophic remodelling in response to chronic hypertensile stress. Migfilin KO mice maintained their cardiac function for a longer time period compared with WT mice, which presented extensive fibrosis and death due to heart failure. Migfilin translocated into the nucleus of TAC-treated cardiomyocytes, and migfilin KO hearts showed reduced Akt activation during the early response to pressure overload. CONCLUSIONS: Our findings indicate an important role of migfilin in the regulation of cardiac hypertrophy upon experimental TAC. |
