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Redox-sensitive prosurvival and proapoptotic protein expression in the myocardial remodeling post-infarction in rats
Paulo Cavalheiro Schenkel1, Angela Maria Vicente Tavares, Rafael Oliveira Fernandes
1Physiology Department, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 Porto Alegre, RS CEP 90050-170, Brazil.
Abstract:
In this study, we investigated the oxidative stress influence in some prosurvival and proapoptotic proteins after myocardial infarction (MI). Male Wistar rats were divided in two groups: Sham-operated (control) and MI. MI was induced by left coronary artery occlusion. 28-days after surgery, echocardiographic, morphometric, and hemodynamic parameters were evaluated. Redox status (reduced to oxidized glutathione ratio, GSH/GSSG) and hydrogen peroxide levels (H(2)O(2)) were measured in heart tissue. The p-ERK/ERK, p-Akt/Akt, p-mTOR/mTOR and p-GSK-3beta/GSK-3beta ratios, as well as apoptosis-inducing factor (AIF) myocardial protein expression were quantified by Western blot. MI group showed an increase in cardiac hypertrophy (23%) associated with a decrease in ejection fraction (38%) and increase in left ventricular end-diastolic pressure (82%) when compared to control, characterizing ventricular dysfunction. Redox status imbalance was seen in MI animals, as evidenced by the decrease in the GSH/GSSG ratio (30%) and increased levels of H(2)O(2) (45%). This group also showed an increase in the ERK phosphorylation and a reduction of Akt and mTOR phosphorylation when compared to control. Moreover, we showed a reduction in the GSK-3beta phosphorylation and an increase in AIF protein expression in MI group. Taken together, our results show increased H(2)O(2) levels and cellular redox imbalance associated to a higher p-ERK and AIF immunocontent, which would contribute to a maladaptive hypertrophy phenotype.
Insights
Myocardial infarction (MI) causes cardiac hypertrophy and dysfunction. This study reveals that increased hydrogen peroxide (H2O2) and redox imbalance in MI hearts are linked to altered protein signaling, promoting maladaptive hypertrophy.
Area of Science:
- Cardiology
- Biochemistry
- Molecular Biology
Background:
- Myocardial infarction (MI) leads to significant cardiac remodeling and dysfunction.
- Oxidative stress plays a critical role in the progression of heart disease post-MI.
- Understanding the molecular mechanisms involving prosurvival and proapoptotic proteins is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the influence of oxidative stress on prosurvival and proapoptotic protein signaling pathways after myocardial infarction (MI) in a rat model.
- To correlate changes in redox status with cardiac hypertrophy and ventricular dysfunction.
Main Methods:
- Induction of MI in male Wistar rats via left coronary artery occlusion.
- Assessment of cardiac function using echocardiography and hemodynamic measurements 28 days post-surgery.
- Quantification of redox status (GSH/GSSG ratio, H2O2 levels) and protein expression (p-ERK/ERK, p-Akt/Akt, p-mTOR/mTOR, p-GSK-3beta/GSK-3beta, AIF) via Western blot.
Main Results:
- MI group exhibited cardiac hypertrophy, reduced ejection fraction, and increased left ventricular end-diastolic pressure, indicating ventricular dysfunction.
- Significant redox status imbalance was observed, with decreased GSH/GSSG ratio and elevated H2O2 levels in MI hearts.
- MI led to increased ERK phosphorylation, reduced Akt and mTOR phosphorylation, decreased GSK-3beta phosphorylation, and elevated apoptosis-inducing factor (AIF) protein expression.
Conclusions:
- Myocardial infarction induces cellular redox imbalance and increases hydrogen peroxide levels.
- Elevated p-ERK and AIF immunocontent, alongside redox imbalance, contribute to the development of maladaptive cardiac hypertrophy post-MI.
- These findings highlight the critical role of oxidative stress in mediating cardiac remodeling after infarction.