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Updated: Oct 20, 2025
Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration
Published on: May 24, 2016
miR-145 transgenic mice develop cardiopulmonary complications leading to postnatal death
Shelby Thomas1, Sathiyanarayanan Manivannan1, Dwitiya Sawant1
1Center for Cardiovascular Research and The Heart Center, Nationwide Children's Hospital, Columbus, Ohio, USA.
Background:
Both downregulation and elevation of microRNA miR-145 has been linked to an array of cardiopulmonary phenotypes, and a host of studies suggest that it is an important contributor in governing the differentiation of cardiac and vascular smooth muscle cell types.
Methods And Results:
To better understand the role of elevated miR-145 in utero within the cardiopulmonary system, we utilized a transgene to overexpress miR-145 embryonically in mice and examined the consequences of this lineage-restricted enhanced expression. Overexpression of miR-145 has detrimental effects that manifest after birth as overexpressor mice are unable to survive beyond postnatal day 18. The miR-145 expressing mice exhibit respiratory distress and fail to thrive. Gross analysis revealed an enlarged right ventricle, and pulmonary dysplasia with vascular hypertrophy. Single cell sequencing of RNA derived from lungs of control and miR-145 transgenic mice demonstrated that miR-145 overexpression had global effects on the lung with an increase in immune cells and evidence of leukocyte extravasation associated with vascular inflammation.
Conclusions:
These data provide novel findings that demonstrate a pathological role for miR-145 in the cardiopulmonary system that extends beyond its normal function in governing smooth muscle differentiation.
Insights
Elevated microRNA 145 (miR-145) during development causes severe cardiopulmonary issues in mice, leading to respiratory distress and early death. This suggests miR-145 has a pathological role beyond smooth muscle development.
Area of Science:
- Cardiovascular Biology
- Pulmonary Medicine
- Developmental Biology
Background:
- MicroRNA miR-145 is implicated in various cardiopulmonary phenotypes.
- Studies suggest miR-145 regulates cardiac and vascular smooth muscle cell differentiation.
Purpose of the Study:
- To investigate the effects of elevated miR-145 in utero on the cardiopulmonary system.
- To examine the consequences of embryonic, lineage-restricted miR-145 overexpression in mice.
Main Methods:
- Utilized a transgenic mouse model for embryonic miR-145 overexpression.
- Examined consequences of enhanced miR-145 expression on survival and cardiopulmonary development.
- Performed gross analysis and single-cell RNA sequencing on lung tissue.
Main Results:
- miR-145 overexpression resulted in postnatal lethality by day 18.
- Overexpressing mice showed respiratory distress, failure to thrive, enlarged right ventricle, and pulmonary dysplasia with vascular hypertrophy.
- Single-cell sequencing revealed global lung effects, increased immune cells, and vascular inflammation.
Conclusions:
- Embryonic miR-145 overexpression has detrimental effects on the cardiopulmonary system.
- These findings demonstrate a pathological role for miR-145 in the cardiopulmonary system.
- This role extends beyond its known function in smooth muscle differentiation.
