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Patients with abdominal aortic aneurysms have reduced levels of microRNA 122-5p in circulating exosomes

OBJECTIVE: There are currently no specific biomarkers to identify patients with abdominal aortic aneurysms (AAAs). Circulating exosomes contain microRNAs (miRNA) that are potential biomarkers for the presence of disease. This study aimed to characterize the exosomal miRNA expression profile of patie...

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Autores principales: Lopez, Jose L., Ramirez, Joel L., Phu, Tuan Anh, Duong, Phat, Bouchareychas, Laura, Kuhrau, Christina R., Lin, Pei-Yu, Eckalbar, Walter L., Barczak, Andrea J., Rudolph, Joshua D., Maliskova, Lenka, Conte, Michael S., Vartanian, Shant M., Raffai, Robert L., Oskowitz, Adam Z.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9928131/
https://www.ncbi.nlm.nih.gov/pubmed/36787323
http://dx.doi.org/10.1371/journal.pone.0281371
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author Lopez, Jose L.
Ramirez, Joel L.
Phu, Tuan Anh
Duong, Phat
Bouchareychas, Laura
Kuhrau, Christina R.
Lin, Pei-Yu
Eckalbar, Walter L.
Barczak, Andrea J.
Rudolph, Joshua D.
Maliskova, Lenka
Conte, Michael S.
Vartanian, Shant M.
Raffai, Robert L.
Oskowitz, Adam Z.
author_facet Lopez, Jose L.
Ramirez, Joel L.
Phu, Tuan Anh
Duong, Phat
Bouchareychas, Laura
Kuhrau, Christina R.
Lin, Pei-Yu
Eckalbar, Walter L.
Barczak, Andrea J.
Rudolph, Joshua D.
Maliskova, Lenka
Conte, Michael S.
Vartanian, Shant M.
Raffai, Robert L.
Oskowitz, Adam Z.
author_sort Lopez, Jose L.
collection PubMed
description OBJECTIVE: There are currently no specific biomarkers to identify patients with abdominal aortic aneurysms (AAAs). Circulating exosomes contain microRNAs (miRNA) that are potential biomarkers for the presence of disease. This study aimed to characterize the exosomal miRNA expression profile of patients with AAAs in order to identify novel biomarkers of disease. METHODS: Patients undergoing duplex ultrasound (US) or computed tomography (CT) for screening or surveillance of an AAA were screened to participate in the study. Cases with AAA were defined as having a max aortic diameter >3 cm. Circulating plasma exosomes were isolated using Cushioned-Density Gradient Ultracentrifugation and total RNA was extracted. Next Generation Sequencing was performed on the Illumina HiSeq4000 SE50. Differential miRNA expression analysis was performed using DESeq2 software with a Benjamini-Hochberg correction. MicroRNA expression profiles were validated by Quantitative Real-Time PCR. RESULTS: A total of 109 patients were screened to participate in the study. Eleven patients with AAA and 15 non-aneurysmal controls met study criteria and were enrolled. Ultrasound measured aortic diameter was significantly larger in the AAA group (mean maximum diameter 4.3 vs 2.0 cm, P = 6.45x10(-6)). More AAA patients had coronary artery disease (5/11 vs 1/15, P = 0.05) as compared to controls, but the groups did not differ significantly in the rates of peripheral arterial disease and chronic obstructive pulmonary disease. A total of 40 miRNAs were differentially expressed (P<0.05). Of these, 18 miRNAs were downregulated and 22 were upregulated in the AAA group compared to controls. After false discovery rate (FDR) adjustment, only miR-122-5p was expressed at significantly different levels in the AAA group compared to controls (fold change = 5.03 controls vs AAA; raw P = 1.8x10(-5); FDR P = 0.02). CONCLUSION: Plasma exosomes from AAA patients have significantly reduced levels of miRNA-122-5p compared to controls. This is a novel exosome-associated miRNA that warrants further investigation to determine its use as a diagnostic biomarker and potential implications in AAA pathogenesis.
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spelling pubmed-99281312023-02-15 Patients with abdominal aortic aneurysms have reduced levels of microRNA 122-5p in circulating exosomes Lopez, Jose L. Ramirez, Joel L. Phu, Tuan Anh Duong, Phat Bouchareychas, Laura Kuhrau, Christina R. Lin, Pei-Yu Eckalbar, Walter L. Barczak, Andrea J. Rudolph, Joshua D. Maliskova, Lenka Conte, Michael S. Vartanian, Shant M. Raffai, Robert L. Oskowitz, Adam Z. PLoS One Research Article OBJECTIVE: There are currently no specific biomarkers to identify patients with abdominal aortic aneurysms (AAAs). Circulating exosomes contain microRNAs (miRNA) that are potential biomarkers for the presence of disease. This study aimed to characterize the exosomal miRNA expression profile of patients with AAAs in order to identify novel biomarkers of disease. METHODS: Patients undergoing duplex ultrasound (US) or computed tomography (CT) for screening or surveillance of an AAA were screened to participate in the study. Cases with AAA were defined as having a max aortic diameter >3 cm. Circulating plasma exosomes were isolated using Cushioned-Density Gradient Ultracentrifugation and total RNA was extracted. Next Generation Sequencing was performed on the Illumina HiSeq4000 SE50. Differential miRNA expression analysis was performed using DESeq2 software with a Benjamini-Hochberg correction. MicroRNA expression profiles were validated by Quantitative Real-Time PCR. RESULTS: A total of 109 patients were screened to participate in the study. Eleven patients with AAA and 15 non-aneurysmal controls met study criteria and were enrolled. Ultrasound measured aortic diameter was significantly larger in the AAA group (mean maximum diameter 4.3 vs 2.0 cm, P = 6.45x10(-6)). More AAA patients had coronary artery disease (5/11 vs 1/15, P = 0.05) as compared to controls, but the groups did not differ significantly in the rates of peripheral arterial disease and chronic obstructive pulmonary disease. A total of 40 miRNAs were differentially expressed (P<0.05). Of these, 18 miRNAs were downregulated and 22 were upregulated in the AAA group compared to controls. After false discovery rate (FDR) adjustment, only miR-122-5p was expressed at significantly different levels in the AAA group compared to controls (fold change = 5.03 controls vs AAA; raw P = 1.8x10(-5); FDR P = 0.02). CONCLUSION: Plasma exosomes from AAA patients have significantly reduced levels of miRNA-122-5p compared to controls. This is a novel exosome-associated miRNA that warrants further investigation to determine its use as a diagnostic biomarker and potential implications in AAA pathogenesis. Public Library of Science 2023-02-14 /pmc/articles/PMC9928131/ /pubmed/36787323 http://dx.doi.org/10.1371/journal.pone.0281371 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Lopez, Jose L.
Ramirez, Joel L.
Phu, Tuan Anh
Duong, Phat
Bouchareychas, Laura
Kuhrau, Christina R.
Lin, Pei-Yu
Eckalbar, Walter L.
Barczak, Andrea J.
Rudolph, Joshua D.
Maliskova, Lenka
Conte, Michael S.
Vartanian, Shant M.
Raffai, Robert L.
Oskowitz, Adam Z.
Patients with abdominal aortic aneurysms have reduced levels of microRNA 122-5p in circulating exosomes
title Patients with abdominal aortic aneurysms have reduced levels of microRNA 122-5p in circulating exosomes
title_full Patients with abdominal aortic aneurysms have reduced levels of microRNA 122-5p in circulating exosomes
title_fullStr Patients with abdominal aortic aneurysms have reduced levels of microRNA 122-5p in circulating exosomes
title_full_unstemmed Patients with abdominal aortic aneurysms have reduced levels of microRNA 122-5p in circulating exosomes
title_short Patients with abdominal aortic aneurysms have reduced levels of microRNA 122-5p in circulating exosomes
title_sort patients with abdominal aortic aneurysms have reduced levels of microrna 122-5p in circulating exosomes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9928131/
https://www.ncbi.nlm.nih.gov/pubmed/36787323
http://dx.doi.org/10.1371/journal.pone.0281371
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