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Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
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Mitochondrial Telomerase Reverse Transcriptase Protects From Myocardial Ischemia/Reperfusion Injury by Improving
Niloofar Ale-Agha1, Philipp Jakobs1, Christine Goy1,2
1Environmentally-induced Cardiovascular Degeneration, Clinical Chemistry and Laboratory Diagnostics (N.A.-A., P,J., C.G., M.Z., J.R., N.D.-R., J.G., F.v.A., O.E., J.A., J.H.), University Hospital and Heinrich-Heine University, Düsseldorf, Germany.
Circulation
|October 21, 2021
Summary
Mitochondrial telomerase reverse transcriptase (TERT) protects the heart from injury by improving mitochondrial function and reducing infarct size. Increasing mitochondrial TERT may offer a new therapeutic approach for cardioprotection.
Area of Science:
- Cardiovascular Biology
- Mitochondrial Medicine
- Telomere Biology
Background:
- Telomerase reverse transcriptase (TERT) has known cardiovascular protective functions.
- TERT localizes to both the nucleus and mitochondria, but its specific roles in each compartment are unclear.
- Existing research lacks tools to differentiate nuclear vs. mitochondrial TERT functions.
Purpose of the Study:
- To elucidate the distinct roles of nuclear and mitochondrial TERT in cardiovascular protection.
- To investigate the impact of mitochondrial TERT on cardiac function and injury response.
- To explore the therapeutic potential of targeting mitochondrial TERT.
Main Methods:
- Generated novel mouse models with exclusive mitochondrial (mitoTERT) or nuclear (nucTERT) TERT expression.
- Assessed outcomes following ischemia/reperfusion injury.
- Evaluated mitochondrial respiration, cardiomyocyte apoptosis, myofibroblast differentiation, and endothelial cell function.
- Analyzed mitochondrial complex I subunit composition.
Main Results:
- Mitochondrial TERT (mitoTERT) enhanced cardiac mitochondrial respiration and reduced infarct size and ejection fraction decline post-ischemia/reperfusion.
- Nuclear TERT (nucTERT) did not confer protection and TERT deficiency impaired mitochondrial respiration.
- mitoTERT improved cardiomyocyte survival, myofibroblast differentiation, and endothelial cell migration.
- TERT was found in human heart mitochondria and increased by ischemic preconditioning.
Conclusions:
- Mitochondrial TERT, not nuclear TERT, is crucial for mitochondrial respiration and protection against ischemia/reperfusion injury.
- Mitochondrial TERT enhances complex I function and confers cardioprotection.
- Elevating mitochondrial TERT levels presents a promising therapeutic strategy for cardiovascular diseases.
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