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Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease
Published on: July 3, 2018
Comparative mRNA and MicroRNA Profiling during Acute Myocardial Infarction Induced by Coronary Occlusion and Ablation
Eduardo T Santana1, Regiane Dos Santos Feliciano2, Andrey J Serra3
1Rehabilitation Department, Universidade Nove de Julho São Paulo, Brazil.
Abstract:
The ligation of the left anterior descending coronary artery is the most commonly used experimental model to induce myocardial infarction (MI) in rodents. A high mortality in the acute phase and the heterogeneity of the size of the MI obtained are drawbacks recognized in this model. In an attempt to solve the problem, our group recently developed a new MI experimental model which is based on application of myocardial ablation radio-frequency currents (AB-RF) that yielded MI with homogeneous sizes and significantly reduce acute mortality. In addition, cardiac structural, and functional changes aroused by AB-RF were similar to those seen in animals with MI induced by coronary artery ligation. Herein, we compared mRNA expression of genes that govern post-MI milieu in occlusion and ablation models. We analyzed 48 mRNAs expressions of nine different signal transduction pathways (cell survival and metabolism signs, matrix extracellular, cell cycle, oxidative stress, apoptosis, calcium signaling, hypertrophy markers, angiogenesis, and inflammation) in rat left ventricle 1 week after MI generated by both coronary occlusion and AB-RF. Furthermore, high-throughput miRNA analysis was also assessed in both MI procedures. Interestingly, mRNA expression levels and miRNA expressions showed strong similarities between both models after MI, with few specificities in each model, activating similar signal transduction pathways. To our knowledge, this is the first comparison of genomic alterations of mRNA and miRNA contents after two different MI procedures and identifies key signaling regulators modulating the pathophysiology of these two models that might culminate in heart failure. Furthermore, these analyses may contribute with the current knowledge concerning transcriptional and post-transcriptional changes of AB-RF protocol, arising as an alternative and effective MI method that reproduces most changes seem in coronary occlusion.
Insights
A new radio-frequency ablation method for inducing myocardial infarction (MI) in rodents offers a more homogeneous infarct size and lower mortality compared to traditional coronary artery ligation. Both methods activate similar molecular pathways, suggesting AB-RF is a viable alternative for MI research.
Area of Science:
- Cardiovascular Research
- Experimental Models
- Molecular Biology
Background:
- Coronary artery ligation is a standard method for inducing myocardial infarction (MI) in rodents.
- This model is associated with high acute mortality and variable infarct sizes.
- There is a need for improved experimental models of MI.
Purpose of the Study:
- To compare the molecular changes induced by a novel myocardial ablation radio-frequency (AB-RF) method with traditional coronary artery ligation for MI.
- To assess the similarities and differences in gene and miRNA expression between the two MI models.
Main Methods:
- Myocardial infarction was induced in rats using either coronary artery ligation or AB-RF.
- mRNA expression of 48 genes across nine signaling pathways was analyzed one week post-MI.
- High-throughput miRNA analysis was performed on both groups.
Main Results:
- Both MI models induced similar cardiac structural and functional changes.
- mRNA and miRNA expression profiles showed significant similarities between the AB-RF and ligation groups.
- Few specific molecular differences were noted, with both models activating comparable signal transduction pathways.
Conclusions:
- The AB-RF method is a viable and effective alternative for inducing MI in experimental settings.
- AB-RF reproduces key pathophysiological changes seen in coronary ligation models with reduced mortality and heterogeneity.
- This study provides insights into the genomic alterations and signaling pathways involved in MI, aiding future research into heart failure.

