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Increased expression of protein kinase C isoforms in heart failure due to myocardial infarction
Jingwei Wang1, Xueliang Liu, Emmanuelle Sentex
1Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada R2H 2A6.
Insights
Cardiac protein kinase C (PKC) activity and isozyme expression increase after myocardial infarction (MI). The angiotensin-converting enzyme inhibitor imidapril partially reversed these changes, suggesting a role for PKC in heart dysfunction post-MI.
Area of Science:
- Cardiology
- Molecular Biology
- Pharmacology
Background:
- Myocardial infarction (MI) leads to cardiac dysfunction.
- Protein Kinase C (PKC) plays a role in cardiac function and pathology.
- Understanding PKC alterations post-MI is crucial for therapeutic development.
Purpose of the Study:
- To investigate the changes in cardiac PKC activity and isozyme expression following myocardial infarction (MI).
- To evaluate the effect of imidapril, an angiotensin-converting enzyme inhibitor, on these PKC alterations.
- To explore the potential role of PKC in cardiac dysfunction post-MI and its modulation by imidapril.
Main Methods:
- Hemodynamic assessment in rats post-MI.
- Measurement of Ca(2+)-dependent and Ca(2+)-independent PKC activities in cardiac tissue.
- Quantification of PKC isozyme (alpha, beta, epsilon, zeta) protein content in cytosolic and particulate fractions.
- Assessment of imidapril treatment effects on PKC parameters and cardiac function.
Main Results:
- PKC activity significantly increased in both left and right ventricles at 1, 2, 4, and 8 weeks post-MI.
- Increased protein content of PKC-alpha, -beta, -epsilon, and -zeta isozymes observed in the failing left ventricle.
- Imidapril treatment partially corrected the altered PKC activities and isozyme levels in infarcted hearts.
- No significant changes in Protein Kinase A activity or content were detected.
Conclusions:
- Increased cardiac PKC activity and altered isozyme expression (PKC-alpha, -beta, -epsilon) are associated with cardiac dysfunction after MI.
- Imidapril may improve heart function post-MI by partially preventing detrimental changes in PKC activity and isozyme content.
- Targeting PKC pathways could be a therapeutic strategy for managing heart failure following myocardial infarction.
Abstract:
The activities of cardiac protein kinase C (PKC) were examined in hemodynamically assessed rats subsequent to myocardial infarction (MI). Both Ca(2+)-dependent and Ca(2+)-independent PKC activities increased significantly in left ventricular (LV) and right ventricular (RV) homogenates at 1, 2, 4, and 8 wk after MI was induced. PKC activities were also increased in both LV and RV cytosolic and particulate fractions from 8-wk infarcted rats. The relative protein contents of PKC-alpha, -beta, -epsilon, and -zeta isozymes were significantly increased in LV homogenate, cytosolic (except PKC-alpha), and particulate fractions from the failing rats. On the other hand, the protein contents of PKC-alpha, -beta, and -epsilon isozymes, unlike the PKC-zeta isozyme, were increased in RV homogenate and cytosolic fractions, whereas the RV particulate fraction showed an increase in the PKC-alpha isozyme only. These changes in the LV and RV PKC activities and protein contents in the 8-wk infarcted animals were partially corrected by treatment with the angiotensin-converting enzyme inhibitor imidapril. No changes in protein kinase A activity and its protein content were seen in the 8-wk infarcted hearts. The results suggest that the increased PKC activity in cardiac dysfunction due to MI may be associated with an increase in the expression of PKC-alpha, -beta, and -epsilon isozymes, and the improvement of heart function in the infarcted animals by imidapril may be due to partial prevention of changes in PKC activity and isozyme contents.