The Long Noncoding RNA CAREL Controls Cardiac Regeneration

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Regenerative Medicine

Background:

• Adult mammalian hearts lack regeneration post-ischemic injury due to inhibited cardiomyocyte mitosis.
• The molecular basis for cardiomyocyte post-mitotic status remains largely unknown.

Purpose of the Study:

• To investigate the role of long noncoding RNAs (lncRNAs) in heart regeneration.
• To define the function of lncRNA CAREL in postnatal and adult cardiac injury.

Main Methods:

• Utilized cardiomyocyte-specific lncRNA-CAREL transgenic mice.
• Employed adenovirus-mediated in vivo silencing of endogenous CAREL.
• Assessed cardiomyocyte replication and heart regeneration via mitosis and cytokinesis assays.

Main Results:

• lncRNA CAREL is upregulated in neonatal cardiomyocytes, correlating with lost regeneration.
• Overexpression of CAREL inhibited cardiomyocyte proliferation and neonatal heart regeneration.
• Silencing CAREL promoted cardiac regeneration and improved function in both neonatal and adult mice after myocardial infarction.
• CAREL acts as a competing endogenous RNA for miR-296, derepressing Trp53inp1 and Itm2a.

Conclusions:

• lncRNA CAREL negatively regulates cardiomyocyte proliferation and heart regeneration.
• CAREL's mechanism involves acting as a competing endogenous RNA for miR-296.
• Targeting CAREL presents a potential strategy for enhancing cardiac repair after injury.