Changes in gene expression patterns in postmortem human myocardial infarction

  • 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.
Author:Verena WilmesGND, Constantin Peter LuxGND, Constanze NiessGND, Elise GradhandORCiDGND, Marcel A. VerhoffORCiDGND, Silke KaufersteinORCiDGND
Parent Title (English):International journal of legal medicine
Place of publication:Berlin ; Heidelberg
Document Type:Article
Date of Publication (online):2020/05/12
Date of first Publication:2020/05/12
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/07/05
Tag:Hypoxia; Hypoxia-inducible factor-1α (HIF-1α); Inducible nitric oxide synthase (iNOS); Myocardial infarction (MI); Transcription regulation; Vascular endothelial growth factor (VEGF)
Page Number:11
First Page:1753
Last Page:1763
Open Access funding provided by Projekt DEAL.
This work is supported by the German Heart Foundation/German Foundation of Heart Research.
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0