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Updated: Dec 21, 2025

Murine Myocardial Infarction Model using Permanent Ligation of Left Anterior Descending Coronary Artery
Published on: August 16, 2019
Changes in gene expression patterns in postmortem human myocardial infarction
Verena Wilmes1, Constantin Lux2, Constanze Niess2
1Institute of Legal Medicine, Johann Wolfgang Goethe University, Frankfurt, Germany. wilmes@med.uni-frankfurt.de.
Abstract:
In murine models, the expression of inducible nitric oxide synthase (iNOS) in myocardial infarction (MI) has been reported to be the result of tissue injury and inflammation. In the present study, mRNA expression of iNOS, hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF) was investigated in postmortem human infarction hearts. Since HIF-1α is the inducible subunit of the transcription factor HIF-1, which regulates transcription of iNOS and VEGF, the interrelation between the three genes was observed, to examine the molecular processes during the emergence of MI. iNOS and VEGF mRNAs were found to be significantly upregulated in the affected regions of MI hearts in comparison to healthy controls. Upregulation of HIF-1α was also present but not significant. Correlation analysis of the three genes indicated a stronger and significant correlation between HIF-1α and iNOS mRNAs than between HIF-1α and VEGF. The results of the study revealed differences in the expression patterns of HIF-1 downstream targets. The stronger transcription of iNOS by HIF-1 in the affected regions of MI hearts may represent a pathological process, since no correlation of iNOS and HIF-1α mRNA was found in non-affected areas of MI hearts. Oxidative stress is considered to cause molecular changes in MI, leading to increased iNOS expression. Therefore, it may also represent a forensic marker for detection of early changes in heart tissue.
Insights
Investigating myocardial infarction (MI) in human hearts, this study found increased expression of inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) in affected areas. Hypoxia-inducible factor-1α (HIF-1α) showed a stronger correlation with iNOS, suggesting a potential forensic marker for early MI detection.
Area of Science:
- Cardiovascular Pathology
- Molecular Biology
- Forensic Medicine
Background:
- Inducible nitric oxide synthase (iNOS) expression in myocardial infarction (MI) is linked to tissue injury and inflammation in murine models.
- Hypoxia-inducible factor-1α (HIF-1α) regulates key genes like iNOS and vascular endothelial growth factor (VEGF).
Purpose of the Study:
- To investigate the mRNA expression of iNOS, HIF-1α, and VEGF in postmortem human infarction hearts.
- To examine the interrelation between these genes and understand molecular processes during MI emergence.
- To explore the potential of iNOS as a forensic marker for early MI detection.
Main Methods:
- Analysis of mRNA expression of iNOS, HIF-1α, and VEGF in postmortem human hearts with and without MI.
- Correlation analysis to determine the interrelationship between the expression levels of the three genes.
- Comparison of gene expression patterns in affected versus non-affected regions of MI hearts.
Main Results:
- Significant upregulation of iNOS and VEGF mRNA was observed in the affected regions of MI hearts compared to controls.
- Upregulation of HIF-1α mRNA was present but not statistically significant.
- A stronger and significant correlation was found between HIF-1α and iNOS mRNA than between HIF-1α and VEGF mRNA in affected areas.
Conclusions:
- The study reveals distinct expression patterns of HIF-1 downstream targets in MI hearts.
- Stronger iNOS transcription by HIF-1 in affected MI regions may indicate a pathological process.
- Increased iNOS expression due to oxidative stress in MI could serve as a forensic marker for early cardiac changes.
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