Thyroid hormone-induced cardiac mechano growth factor expression depends on beating activity

Area of Science:

• Cardiovascular Biology
• Molecular Endocrinology
• Muscle Stem Cell Biology

Background:

• Mechano growth factor (MGF), an IGF-I splice variant, is crucial for skeletal muscle stem cell proliferation and hypertrophy.
• MGF exhibits neuroprotective effects and improves cardiac function post-myocardial infarction.
• MGF's role in exercise-induced skeletal muscle hypertrophy suggests potential involvement in cardiac hypertrophy.

Purpose of the Study:

• To investigate the regulation of MGF expression in the heart.
• To determine if MGF is involved in thyroid hormone-induced cardiac hypertrophy.
• To elucidate the mechanical dependence of MGF induction in cardiomyocytes.

Main Methods:

• Induction of physiological cardiac hypertrophy in mice using thyroid hormone (T(3)).
• Analysis of MGF mRNA expression in specific heart regions.
• Isolation and treatment of neonatal rat cardiomyocytes with T(3) and KCl to assess contractile activity and gene expression.

Main Results:

• T(3) treatment increased MGF mRNA expression in mouse heart ventricles and septum.
• MGF expression correlated with heart beating frequency in hyper- and hypothyroid states.
• Cardiomyocyte MGF mRNA upregulation by T(3) was dependent on contractile activity, unlike IGF-IEa.

Conclusions:

• MGF expression in the heart is specifically stimulated by mechanical loading.
• MGF plays a key role in mediating the hypertrophic response to thyroid hormone in the heart.
• Cardiomyocyte beating activity is essential for MGF induction, highlighting a mechanical signaling pathway in cardiac adaptation.