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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1438838
This article is part of the Research Topic Immune Cells, Inflammation, and Cardiovascular Disease: Advancements in Novel Drug Discoveries to Immunotherapeutic Strategies View all 5 articles

Deciphering the causal association and underlying transcriptional mechanisms between telomere length and abdominal aortic aneurysm

Provisionally accepted
Jiyu Zhang Jiyu Zhang Xinyi Xia Xinyi Xia Shujie He Shujie He *
  • Huazhong University of Science and Technology, Wuhan, China

The final, formatted version of the article will be published soon.

    The purpose of this study is to investigate the causal effect and potential mechanisms between telomere length and abdominal aortic aneurysm (AAA).Methods: Summary statistics of telomere length and AAA were derived from IEU open genomewide association studies and FinnGen R9, respectively. Bi-directional Mendelian randomization (MR) analysis was conducted to reveal the causal relationship between AAA and telomere length. Three transcriptome datasets were retrieved from the Gene Expression Omnibus database and telomere related genes was down-loaded from TelNet. The overlapping genes of AAA related differentially expressed genes (DEGs), module genes, and telomere related genes were used for further investigation. Telomere related diagnostic biomarkers of AAA were selected with machine learning algorisms and validated in datasets and murine AAA model. The correlation between biomarkers and immune infiltration landscape was established.Telomere length was found to have a suggestive negative associations with AAA [IVW, OR 95%CI = 0.558 (0.317-0.701), P < 0.0001], while AAA showed no suggestive effect on telomere length [IVW, OR 95%CI = 0.997 (0.990-1.004), P = 0.4061]. A total of 40 genes was considered as telomere related DEGs of AAA. PLCH2, PRKCQ, and SMG1 were selected as biomarkers after multiple algorithms and validation. Immune infiltration analysis and single cell mRNA analysis revealed that PLCH2 and PRKCQ were mainly expressed on T cells, while SMG1 predominantly expressed on T cells, B cells, and monocytes. Murine AAA model experiments further validated the elevated expression of biomarkers. Conclusion: We found a suggestive effect of telomere length on AAA and revealed the potential biomarkers and immune mechanism of telomere length on AAA. This may shed new light for diagnosis and therapeutics on AAA

    Keywords: Abdominal Aortic Aneurysm, telomere length, Mendelian randomization, Bioinformatic analysis, diagnostic biomarkers

    Received: 26 May 2024; Accepted: 01 Aug 2024.

    Copyright: © 2024 Zhang, Xia and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Shujie He, Huazhong University of Science and Technology, Wuhan, China

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