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Examining the expression levels of ferroptosis-related genes in angiographically determined coronary artery disease patients

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Abstract

Background

Cardiovascular diseases are the leading cause of death worldwide, with several conditions being affected by oxidative stress. Ferroptosis, recently identified programmed cell death mechanism, is relies on oxidative stress. This study aimed to determine the expressions of the genes involved in the molecular pathways of oxidative stress and ferroptosis and the association of these genes with CAD risk factors in CAD and non-CAD individuals.

Methods and results

The blood samples of individuals who underwent coronary angiography were collected and divided according to CAD status. Total RNA isolation was performed using the PAXgene RNA isolation kit from the whole blood samples. The mRNA expression levels of RTN3, GPX4, CAT, HMOX1, ELOVL5, SLC25A1, SLC7A11, and ACSL4 genes were determined using Real-Time PCR. Biochemical analyses were done before coronary angiography, and the results were evaluated statistically. The expression levels of the CAT gene are significantly lower in the CAD group when compared to non-CAD. HMOX1 expression levels are positively correlated with stenosis percentage, Gensini, and SYNTAX scores in the CAD group. RTN3, SLC25A1, and GPX4 mRNA expressions are correlated with HDL-C levels. Moreover, HbA1c levels and BMI, correlate negatively with ACSL4 expression in non-CAD controls. Also, ELOVL5 expression is negatively correlated with total bilirubin and direct bilirubin levels in the CAD group.

Conclusions

In this study, the genes related to oxidative stress and ferroptosis were found associated with biochemical parameters associated with CAD risk. These preliminary results may provide a new perspective to further studies investigating the reasons behind the identified associations.

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Funding

This study was funded by Scientific Research Projects Coordination Unit of Istanbul University. Project Number: 34037 and 25862.

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Authors

Contributions

ASO: Conceptualization, formal analysis, investigation, writing-original draft, writing—review and editing, visualization; AFE: Methodology, investigation, resources, writing—review and editing; NC: Conceptualization, methodology, investigation, resources, writing—review and editing, supervision, project administration, funding acquisition; NU: Conceptualization, methodology, resources, writing—review and editing, supervision, project administration, funding acquisition.

Corresponding authors

Correspondence to Neslihan Coban or Nihan Unaltuna.

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Conflict of interest

The authors declare no competing interests. The authors have no competing interests to declare that are relevant to the content of this article.

Ethical approval

Whole sample collection and analysis processes were conducted in compliance with the ethical guidelines of the Declaration of Helsinki and approved by the Institutional Review Board at Istanbul University (Approval date: 14.12.2018, no:1738).

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The written informed consent was obtained from all participants, and all experiments were performed following the approved guidelines and regulations.

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Ozuynuk, A.S., Erkan, A.F., Coban, N. et al. Examining the expression levels of ferroptosis-related genes in angiographically determined coronary artery disease patients. Mol Biol Rep 49, 7677–7686 (2022). https://doi.org/10.1007/s11033-022-07583-y

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