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Role of lncRNAs in Remodeling of the Coronary Artery Plaques in Patients with Atherosclerosis

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Abstract

Introduction

Cardiovascular diseases (CVDs) are the leading cause of death worldwide according to World Health Organization (WHO) data. Atherosclerosis is considered as a chronic inflammatory disease that develops in response to damage to the vascular intima-media layer in most cases. In recent years, epigenetic events have emerged as important players in the development and progression of CVDs. Since noncoding RNA (ncRNAs) are important regulators in the organization of the pathophysiological processes of the cardiovascular system, they have the potential to be used as therapeutic targets, diagnostic and prognostic biomarkers. In this study long noncoding RNA (lncRNA) and mRNA gene expression were compared between coronary atherosclerotic plaques (CAP) and the internal mammary artery (IMA)  which has the same genetic makeup and is exposed to the same environmental stress conditions with CAP in the same individual.

Methods

lncRNA and mRNA gene expressions were determined using the microarray in the samples. Microarray results were validated by RT-qPCR. Differentially expressed genes (DEGs; lncRNAs and mRNAs) were determined by GeneSpring (Ver 3.0) [p values < 0.05 and fold change (FC) > 2]. DAVID bioinformatics program was used for Gene Ontology (GO) annotation and enrichment analyses of statistically significant genes between CAP and IMA tissue.

Results and Conclusions

In our study, 345 DEGs were found to be statistically significant (p < 0.05; FC > 2) between CAP and IMA. Of these, 65 were lncRNA and 280 were mRNA. Thirty-three lncRNAs were upregulated, while 32 lncRNAs were downregulated. Some of the important mRNAs are SPP1, CYP4B1, CHRDL1, MYOC, and ALKAL2, while some of the lncRNAs are LOC105377123, LINC01857, DIO3OS, LOC101928134, and KCNA3 between CAP and IMA tissue. We also identified genes that correlated with statistically significant lncRNAs. The results of this study are expected to be an important source of data in the development of new genetically based drugs to prevent atherosclerotic plaque. In addition, the data obtained may contribute to the explanation of the epigenetic mechanisms that play a role in the pathological basis of the process that protects the IMA from atherosclerosis.

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Author information

Authors and Affiliations

  1. Department of Medical Biology, Faculty of Medicine, Mersin University, 33343, Mersin, Turkey

    Serdal Arslan

  2. Department of Molecular Biology and Genetics, Faculty of Science, Sivas Cumhuriyet University, 58140, Sivas, Turkey

    Nil Özbilum Şahin

  3. Department of Medical Biology, Faculty of Medicine, Sivas Cumhuriyet University, 58140, Sivas, Turkey

    Burcu Bayyurt

  4. Department of Cardiovascular Surgery, Cigli Regional Training Hospital, Izmir, Turkey

    Öcal Berkan

  5. Department of Cardiology, Faculty of Medicine, Dokuz Eylul University, 35340, Izmir, Turkey

    Mehmet Birhan Yılmaz

  6. Department of Cardiovascular Surgery, SBU Van Training and Research Hospital, 65300, Edremit, Van, Turkey

    Mehmet Aşam

  7. Mersin University Biotechnology Research and Application Center, Mersin University, 33343, Mersin, Turkey

    Furkan Ayaz

  8. Department of Biotechnology, Faculty of Arts and Science, Mersin University, 33343, Mersin, Turkey

    Furkan Ayaz

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  1. Serdal Arslan
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Corresponding authors

Correspondence to Serdal Arslan or Furkan Ayaz.

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Funding

This study was funded by the Scientific Research and Technological Research Council of Turkey (TUBITAK) (project no:218S524).

Conflict of Interest

Serdal Arslan, Nil Özbilüm Şahin, Burcu Bayyurt, Öcal Berkan, Mehmet Birhan Yılmaz, Mehmet Aşam, and Furkan Ayaz declare that they have no conflicts of interest that might be relevant to the contents of this manuscript."

Ethics Approval

In our study, we performed microarray analysis on 32 samples that consisted of 16 IMA and 16 CAP tissue samples taken from Sivas Cumhuriyet University Research Hospital Cardiovascular Surgery Department. The patients had bypass surgery, and the samples were taken from their IMA and CAP tissues on the basis of the ethical permissions (Sivas Cumhuriyet University Clinical Research Ethics Committee decision number: 2018-09/150 and 2018–04/18). The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Written informed consent form was obtained from all volunteers.

Consent (Participation and Publication)

Not applicable.

Author Contri̇buti̇ons

S.A., N.Ö.Ş., and B.B. performed experiments; S.A., N.Ö.Ş., B.B., and F.A. prepared figures; S.A., N.Ö.Ş., B.B., F.A., and M.B.Y. edited and revised manuscript; S.A., N.Ö.Ş., B.B., and F.A. drafted manuscript; S.A., N.Ö.Ş., and B.B. analyzed data; S.A., M.B.Y., and Ö.B. conceived and designed research; M.B.Y., Ö.B., and M.A. performed sample collection and analyzed demographic and clinical parameters.

Code Availability

Not applicable.

Data Availability Statement

Data is available upon reasonable request from the corresponding authors.

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Arslan, S., Şahin, N.Ö., Bayyurt, B. et al. Role of lncRNAs in Remodeling of the Coronary Artery Plaques in Patients with Atherosclerosis. Mol Diagn Ther 27, 601–610 (2023). https://doi.org/10.1007/s40291-023-00659-w

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