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Updated: Feb 6, 2026
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Apical Resection Mouse Model to Study Early Mammalian Heart Regeneration
Published on: January 23, 2016
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CLIPPER Regulates LPIN1-Mediated Mitochondrial Biogenesis and Heart Regeneration
Francesco Ruberto1,2, Daniel Maric1, Tatjana Kleele3,4
1Experimental Cardiology Unit, Division of Cardiology, Department of Cardiovascular Medicine, University of Lausanne Medical School, Switzerland (F.P.R., D.M., M.N., I.P., P.A., T.P.).
Circulation Research
|February 5, 2026
Summary
Researchers identified a novel long noncoding RNA, Clipper, that promotes heart regeneration. Clipper knockdown stimulates cardiomyocyte proliferation and restores heart function after myocardial infarction, offering a potential therapeutic target.
Area of Science:
- Cardiovascular Biology
- Epigenetics
- Mitochondrial Biology
Background:
- The adult mammalian heart has limited regenerative capacity after myocardial infarction, leading to heart failure.
- Regenerating the injured heart by reactivating dormant processes is a key therapeutic goal.
- Newly formed cardiomyocytes in regenerating hearts arise from pre-existing ones.
Purpose of the Study:
- To identify novel regulators of cardiomyocyte proliferation.
- To explore the role of long noncoding RNAs (lncRNAs) in cardiac regeneration.
Main Methods:
- Developed a high-throughput screening assay to identify lncRNAs promoting cardiomyocyte proliferation.
- Identified and characterized the lncRNA *Clipper* and its target gene *Lpin1*.
- Investigated the effects of *Clipper* knockdown on mitochondrial biogenesis and cardiac function in vivo.
Main Results:
- *Clipper* regulates mitochondrial biogenesis via *Lpin1*, influencing mitochondrial division and bioenergetics.
- Silencing *Clipper* or *Lpin1* decreased oxidative metabolism, reduced reactive oxygen species, and dampened DNA damage.
- *Clipper* knockdown in vivo promoted cardiac regeneration and restored heart function post-myocardial infarction.
- *CLIPPER* is conserved in humans, suggesting broad therapeutic potential.
Conclusions:
- *CLIPPER* is a novel therapeutic target for heart regeneration.
- It acts by controlling LPIN1-dependent mitochondrial biogenesis and cardiomyocyte proliferation.
- This study provides a foundation for developing therapies to enhance cardiac repair.
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