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Updated: Apr 29, 2026
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
MicroRNAs associated with ischemia-reperfusion injury and cardioprotection by ischemic pre- and postconditioning:
Zoltán V Varga1, Agnes Zvara2, Nóra Faragó2
1Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged, Hungary; Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary; Pharmahungary Group, Szeged, Hungary.
Abstract:
We aimed to characterize early changes in microRNA expression in acute cardioprotection by ischemic pre- and postconditioning in rat hearts. Hearts isolated from male Wistar rats were subjected to 1) time-matched nonischemic perfusion, 2) ischemia-reperfusion (30 min of coronary occlusion and 120 min of reperfusion), 3) preconditioning (3 × 5 min of coronary occlusion) followed by ischemia-reperfusion, or 4) ischemia-reperfusion with postconditioning (6 × 10 s of global ischemia-reperfusion at the onset of reperfusion). Infarct size was significantly reduced by both interventions. Of 350 different microRNAs assessed by microarray analysis, 147-160 microRNAs showed detectable expression levels. Compared with microRNA alterations induced by ischemia-reperfusion versus time-matched nonischemic controls, five microRNAs were significantly affected by both pre- and postconditioning (microRNA-125b*, microRNA-139-3p, microRNA-320, microRNA-532-3p, and microRNA-188), four microRNAs were significantly affected by preconditioning (microRNA-487b, microRNA-139-5p, microRNA-192, and microRNA-212), and nine microRNAs were significantly affected by postconditioning (microRNA-1, microRNA let-7i, microRNA let-7e, microRNA let-7b, microRNA-181a, microRNA-208, microRNA-328, microRNA-335, and microRNA-503). Expression of randomly selected microRNAs was validated by quantitative real-time PCR. By a systematic comparison of the direction of microRNA expression changes in all groups, we identified microRNAs, specific mimics, or antagomiRs that may have pre- and postconditioning-like cardioprotective effects (protectomiRs). Transfection of selected protectomiRs (mimics of microRNA-139-5p, microRNA-125b*, microRNA let-7b, and inhibitor of microRNA-487b) into cardiac myocytes subjected to simulated ischemia-reperfusion showed a significant cytoprotective effect. This is the first demonstration that the ischemia-reperfusion-induced microRNA expression profile is significantly influenced by both pre- and postconditioning, which shows the involvement of microRNAs in cardioprotective signaling. Moreover, by analysis of microRNA expression patterns in cardioprotection by pre- and postconditioning, specific protectomiRs can be revealed as potential therapeutic tools for the treatment of ischemia-reperfusion injury.
Insights
Ischemic preconditioning and postconditioning protect rat hearts by altering microRNA expression. Researchers identified specific microRNAs (protectomiRs) that mimic these effects, offering potential new therapies for heart injury.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Gene Regulation
Background:
- Ischemic preconditioning and postconditioning are established methods for acute cardioprotection against ischemia-reperfusion injury.
- MicroRNAs (miRNAs) are small non-coding RNAs that play crucial roles in regulating gene expression and cellular processes.
- Understanding miRNA dynamics during cardioprotection is essential for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate early changes in miRNA expression profiles in rat hearts subjected to ischemic preconditioning and postconditioning.
- To identify specific miRNAs that are modulated by these cardioprotective interventions.
- To explore the potential of identified miRNAs as therapeutic targets for ischemia-reperfusion injury.
Main Methods:
- Rat hearts were subjected to different protocols: nonischemic perfusion, ischemia-reperfusion (I/R), preconditioning followed by I/R, and I/R with postconditioning.
- Microarray analysis was used to assess the expression of 350 different miRNAs.
- Quantitative real-time PCR was employed for validation of selected miRNA expression.
- In vitro studies involved transfecting cardiac myocytes with miRNA mimics or inhibitors.
Main Results:
- Both preconditioning and postconditioning significantly reduced infarct size in rat hearts.
- Microarray analysis revealed significant alterations in the expression of numerous miRNAs in response to I/R, preconditioning, and postconditioning.
- Five miRNAs (miR-125b*, miR-139-3p, miR-320, miR-532-3p, miR-188) were commonly affected by both interventions.
- Specific miRNAs were uniquely modulated by preconditioning or postconditioning.
- Transfection with selected miRNA mimics (miR-139-5p, miR-125b*, miR-let-7b) or an inhibitor (anti-miR-487b) demonstrated cytoprotective effects in simulated I/R conditions.
Conclusions:
- This study provides the first evidence that ischemia-reperfusion-induced miRNA expression is significantly influenced by both pre- and postconditioning.
- These findings highlight the critical involvement of miRNAs in cardioprotective signaling pathways.
- Identified miRNAs, termed 'protectomiRs', represent promising therapeutic candidates for mitigating ischemia-reperfusion injury.
