Related Experiment Video
Updated: May 26, 2026
Viral Transgene Expression in Rodent Hearts and the Assessment of Cardiac Arrhythmia Risk
Published on: July 27, 2022
Cardioprotection by Hepc1 in cTnT(R141W) transgenic mice
1Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medical Center, Peking Union Medical College, Panjiayuan Nanli, Chaoyang District, Beijing 100021, People's Republic of China.
Insights
Hepcidin 1 (Hepc1) peptide hormone levels were restored in a mouse model of dilated cardiomyopathy (DCM). This improved heart function, reduced mortality, and mitigated cardiac damage, suggesting Hepc1
Area of Science:
- Cardiovascular Biology
- Iron Metabolism
- Molecular Cardiology
Background:
- Hepcidin 1 (Hepc1) is a liver-secreted peptide hormone regulating iron homeostasis.
- Hepc1 is expressed in the heart, potentially influencing cardiac iron regulation.
- Hepc1 expression is significantly downregulated in a mouse model of dilated cardiomyopathy (DCM).
Purpose of the Study:
- To investigate the therapeutic potential of Hepc1 in a mouse model of DCM.
- To determine the effects of restoring cardiac Hepc1 expression on DCM progression and cardiac function.
Main Methods:
- Generation of transgenic mice with heart tissue-specific Hepc1 expression.
- Introduction of Hepc1 expression into the cTnT(R141W) transgenic DCM mouse model.
- Assessment of cardiac function, mortality, fibrosis, iron levels, and ERK1/2 signaling.
Main Results:
- Transgenic Hepc1 expression was nonlethal and significantly reduced mortality in DCM mice.
- Hepc1 expression improved cardiac function, including left ventricular wall thickness, ejection fraction, and fractional shortening.
- Hepc1 inhibited cardiac fibrosis, normalized iron levels, and restored ERK1/2 phosphorylation in DCM hearts.
Conclusions:
- Restoring cardiac Hepc1 expression significantly ameliorates the DCM phenotype in mice.
- Hepc1 plays a protective role in the heart, counteracting iron dysregulation and cardiac remodeling.
- The ERK1/2 signaling pathway may be a key mediator of Hepc1's beneficial effects in DCM.
Abstract:
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.
