Changes in gene expression patterns in postmortem human myocardial infarction

Verena Wilmes,Elise Gradhand,Constantin Lux,Silke Kauferstein,Constanze Niess,Marcel A Verhoff

doi:10.1007/s00414-020-02311-2

Verena Wilmes, Elise Gradhand + Show 4 more

Open Access

https://doi.org/10.1007/s00414-020-02311-2

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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.

Highlights

Myocardial infarction (MI) is the result of sustained insufficient blood supply to areas of the myocardium [1]
INOS and vascular endothelial growth factor (VEGF) gene expression in the affected regions of MI hearts was found to be significantly increased when compared to healthy control hearts, while Hypoxia-inducible factor-1α (HIF-1α) expression was increased as well, but not significantly
Scatterplot of the monotone relation between HIF-1α and VEGF mRNA in affected regions of MI hearts

Summary

Introduction

Myocardial infarction (MI) is the result of sustained insufficient blood supply to areas of the myocardium [1]. Restoration of the blood flow to the ischemic myocardium causes the generation of reactive oxygen species (ROS) [2], the activation of inflammatory cascades, and the expression of the inducible nitric oxide synthase (iNOS) [1, 3]. In forensic approaches, cardiac oxidative stress is considered to contribute to cardiac death, aggravating postmortem diagnosis [16]. In humans who died of acute exposure to high doses of cocaine, myocardial oxidative damage was found through oxidative stress, accompanied by a

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