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Updated: Dec 3, 2025
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Ameliorating Effect of Klotho Protein on Rat Heart during I/R Injury
Agnieszka Olejnik1, Anna Krzywonos-Zawadzka1, Marta Banaszkiewicz1
1Division of Clinical Chemistry and Laboratory Hematology, Department of Medical Laboratory Diagnostics, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A St., 50-556 Wroclaw, Poland.
Insights
Klotho protein protects the heart from ischaemia/reperfusion (I/R) injury by improving heart function and reducing cell damage. This suggests Klotho may be a potential therapeutic agent for preventing heart contractile dysfunction after I/R events.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Oxidative Stress Research
Background:
- Ischaemia/reperfusion (I/R) injury is a significant complication following myocardial infarction treatment, leading to oxidative stress and cardiac dysfunction.
- Klotho protein, found in heart tissue, is known for its roles in antioxidation and ion homeostasis.
- Understanding Klotho's protective mechanisms against I/R injury is crucial for developing novel cardioprotective strategies.
Purpose of the Study:
- To investigate the protective effects of Klotho protein on heart tissue subjected to I/R injury.
- To determine if Klotho protein administration can ameliorate I/R-induced cardiac dysfunction and oxidative stress.
- To explore the impact of Klotho on contractile protein levels and overall heart function post-I/R.
Main Methods:
- Utilized Wistar rats as an ex vivo heart model and isolated rat cardiomyocytes for in vitro studies.
- Hearts were subjected to global no-flow ischaemia, and cardiomyocytes to chemical I/R, with and without recombinant Klotho protein.
- Assessed haemodynamic parameters, myocyte contractility, I/R injury markers, oxidative stress, and contractile protein levels (MLC1, TnI).
Main Results:
- Klotho protein treatment significantly improved heart mechanical function and myocyte contractility in I/R-injured hearts.
- Administration of Klotho protein reduced tissue injury markers and enhanced the heart's antioxidant capacity.
- Reduced release of contractile proteins, myosin light chain 1 (MLC1) and troponin I (TnI), was observed in Klotho-treated groups.
Conclusions:
- Klotho protein demonstrates a significant cardioprotective role against I/R injury in the rat heart model.
- Klotho protein administration effectively mitigates I/R-induced contractile dysfunction and oxidative stress.
- Klotho protein holds potential as a therapeutic agent for preventing heart damage and dysfunction associated with I/R injury.
Abstract:
An essential procedure for the treatment of myocardial infarction is restoration of blood flow in the obstructed infarct artery, which may cause ischaemia/reperfusion (I/R) injury. Heart I/R injury manifests in oxidative stress, metabolic and morphological disorders, or cardiac contractile dysfunction. Klotho protein was found to be produced in the heart tissue and participate in antioxidation or ion homeostasis. The aim of this study was to examine an influence of Klotho protein on the heart subjected to I/R injury. Wistar rats served as a surrogate heart model ex vivo. Rat hearts perfused using the Langendorff method were subjected to global no-flow ischaemia, and isolated rat cardiomyocytes underwent chemical I/R in vitro, with or without recombinant Klotho protein administration. Haemodynamic parameters of heart function, cell contractility, markers of I/R injury and oxidative stress, and the level of contractile proteins such as myosin light chain 1 (MLC1) and troponin I (TnI) were measured. The treatment of hearts subjected to I/R injury with Klotho protein resulted in a recovery of heart mechanical function and ameliorated myocyte contractility. This improvement was associated with decreased tissue injury, enhanced antioxidant capacity, and reduced release of MLC1 and TnI. The present research showed the contribution of Klotho to cardioprevention during I/R. Thus, Klotho protein may support the protection from I/R injury and prevention of contractile dysfunction in the rat heart.
