| First Author | Zhang L | Year | 2012 |
| Journal | Transgenic Res | Volume | 21 |
| Issue | 4 | Pages | 867-78 |
| PubMed ID | 22198484 | Mgi Jnum | J:186589 |
| Mgi Id | MGI:5432667 | Doi | 10.1007/s11248-011-9582-y |
| Citation | Zhang L, et al. (2012) Cardioprotection by Hepc1 in cTnT(R141W) transgenic mice. Transgenic Res 21(4):867-78 |
| abstractText | Hepcidin 1 (Hepc1) is a peptide hormone secreted by the liver in response to iron loading. It is expressed in the heart and is thought to play a role in the regulation of iron homeostasis in an autocrine and paracrine fashion. We have shown that expression of Hepc1 is strongly down-regulated in the heart of the cTnT(R141W) transgenic mouse model of dilated cardiomyopathy (DCM) at 3 months of age. Transgenic mice with heart tissue-specific Hepc1 expression alone or in combination with the cTnT(R141W) mutation were produced to study the effects of Hepc1 on DCM. Transgenic expression of Hepc1 was found to be nonlethal and resulted in decreased mortality in cTnT(R141W) transgenic mice, from 29.6 to 7.4%(n = 27; P < 0.05), through 7 months of age. Expression of Hepc1 also brought about increases in the left ventricular wall, as well as ejection fraction and fractional shortening. In addition, the expression of Hepc1 inhibited the fibrosis and ultra-structural alterations seen in cTnT(R141W) transgenic mice. Furthermore, transgenic expression of Hepc1 restored the iron level and phosphorylation level of extracellular signal-regulated kinases 1/2 (ERK1/2) in the heart tissues of cTnT(R141W) transgenic mice. It was concluded that transgenic expression of Hepc1 compensated for the loss of Hepc1 expression and the release of iron and brought about a marked improvement in the pathologic phenotype of DCM, in which the ERK1/2 signal pathway might play an important role. |
