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iNOS expressing macrophages co-localize with nitrotyrosine staining after myocardial infarction in humans
Verena Wilmes1, Ivan M Kur2, Andreas Weigert2,3
1Institute of Legal Medicine, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
Introduction:
Inducible nitric oxide synthase (iNOS) produces micromolar amounts of nitric oxide (NO) upon the right stimuli, whose further reactions can lead to oxidative stress. In murine models of myocardial infarction (MI), iNOS is known to be expressed in infiltrating macrophages, which at early onset enter the infarcted zone and are associated with inflammation. In contrast cardiac tissue resident macrophages are thought to enhance regeneration of tissue injury and re-establish homeostasis. Both detrimental and beneficial effects of iNOS have been described, still the role of iNOS in MI is not fully understood. Our aim was to examine cell expression patterns of iNOS and nitrotyrosine (NT) production in human MI.
Material And Methods:
We examined in postmortem human MI hearts the iNOS mRNA expression by means of qPCR. Further we performed immunohistochemical stainings for cell type identification. Afterwards a distance analysis between iNOS and NT was carried out to determine causality between iNOS and NT production.
Results:
iNOS mRNA expression was significantly increased in infarcted regions of human MI hearts and iNOS protein expression was detected in resident macrophages in infarcted human hearts as well as in controls hearts, being higher in resident macrophages in MI hearts compared to control. Furthermore in MI and in healthy human hearts cells showing signs of NT production peaked within 10-15 µm proximity of iNOS+ cells.
Discussion:
These results indicate that, unexpectedly, resident macrophages are the main source of iNOS expression in postmortem human MI hearts. The peak of NT positive cells within 10-15 µm of iNOS+ cells suggest an iNOS dependent level of NT and therefore iNOS dependent oxidative stress. Our results contribute to understanding the role of iNOS in human MI.
Insights
Resident macrophages in human hearts are the primary source of inducible nitric oxide synthase (iNOS), contributing to oxidative stress after myocardial infarction (MI). This finding clarifies the role of iNOS in human heart attacks.
Area of Science:
- Cardiovascular Science
- Immunology
- Molecular Biology
Background:
- Inducible nitric oxide synthase (iNOS) produces nitric oxide (NO), which can cause oxidative stress.
- In myocardial infarction (MI), iNOS is found in infiltrating macrophages, but its role in human hearts is unclear.
- Resident cardiac macrophages are implicated in tissue repair, contrasting with infiltrating macrophages.
Purpose of the Study:
- To investigate the cellular expression patterns of iNOS and nitrotyrosine (NT) in human myocardial infarction (MI).
- To determine the specific cell types responsible for iNOS production in human MI.
- To assess the relationship between iNOS and oxidative stress markers in human MI.
Main Methods:
- Quantitative PCR (qPCR) to measure iNOS mRNA expression in postmortem human MI hearts.
- Immunohistochemistry to identify cell types expressing iNOS protein.
- Spatial analysis to determine the proximity of iNOS-positive cells to nitrotyrosine (NT)-positive cells.
Main Results:
- iNOS mRNA expression was significantly elevated in infarcted regions of human MI hearts.
- iNOS protein was detected in resident macrophages in both MI and control hearts, with higher levels in MI.
- Nitrotyrosine (NT)-positive cells were predominantly found within 10-15 µm of iNOS-positive cells in both MI and healthy hearts.
Conclusions:
- Resident cardiac macrophages are the primary source of iNOS in human MI.
- The close proximity of NT-positive cells to iNOS-positive cells suggests iNOS-dependent oxidative stress in human MI.
- These findings enhance the understanding of iNOS's role in the pathophysiology of human myocardial infarction.
