Tissue and plasma proteomic profiling indicates AHSG as a potential biomarker for ascending thoracic aortic aneurysms

Abstract Background Thoracic Aortic Aneurysms (TAAs) develop asymptomatically and are characterized by dilatation of the aorta. This is considered a life-threatening vascular disorder due to the risk of aortic dissection and rupture. There is an urgent need to identify blood-borne biomarkers for the...

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Main Authors: Rafailia Kazamia, Anna Keravnou, Areti Moushi, Kleitos Sokratous, Kyriaki Michailidou, Kristia Yiangou, Marinos Soteriou, Stavroulla Xenophontos, Marios A. Cariolou, Evy Bashiardes
Format: Article
Language:English
Published: BMC 2023-03-01
Series:BMC Cardiovascular Disorders
Subjects:
Online Access:https://doi.org/10.1186/s12872-023-03154-6
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author Rafailia Kazamia
Anna Keravnou
Areti Moushi
Kleitos Sokratous
Kyriaki Michailidou
Kristia Yiangou
Marinos Soteriou
Stavroulla Xenophontos
Marios A. Cariolou
Evy Bashiardes
author_facet Rafailia Kazamia
Anna Keravnou
Areti Moushi
Kleitos Sokratous
Kyriaki Michailidou
Kristia Yiangou
Marinos Soteriou
Stavroulla Xenophontos
Marios A. Cariolou
Evy Bashiardes
author_sort Rafailia Kazamia
collection DOAJ
description Abstract Background Thoracic Aortic Aneurysms (TAAs) develop asymptomatically and are characterized by dilatation of the aorta. This is considered a life-threatening vascular disorder due to the risk of aortic dissection and rupture. There is an urgent need to identify blood-borne biomarkers for the early detection of TAA. The goal of the present study was to identify potential protein biomarkers associated with TAAs, using proteomic analysis of aortic tissue and plasma samples. Methods Extracted proteins from 14 aneurysmal and 12 non-aneurysmal thoracic aortic tissue specimens as well as plasma samples from six TAA patients collected pre-and postoperatively and six healthy controls (HC), were analyzed by liquid chromatography-tandem mass spectrometry. Proteomic data were further processed and following filtering criteria, one protein was selected for verification and validation in a larger cohort of patients and controls using a targeted quantitative proteomic approach and enzyme-linked immunosorbent assay, respectively. Results A total of 1593 and 363 differentially expressed proteins were identified in tissue and plasma samples, respectively. Pathway enrichment analysis on the differentially expressed proteins revealed a number of dysregulated molecular pathways that might be implicated in aneurysm pathology including complement and coagulation cascades, focal adhesion, and extracellular matrix receptor interaction pathways. Alpha-2-HS glycoprotein (AHSG) was selected for further verification in 36 TAA and 21 HC plasma samples using targeted quantitative proteomic approach. The results showed a significantly decreased concentration of AHSG (p = 0.0002) in the preoperative plasma samples compared with HC samples. Further analyses using a larger validation dataset revealed that AHSG protein levels were significantly lower (p = 0.03) compared with HC. Logistic regression analysis on the validation dataset revealed males, advanced age, hypertension and hyperlipidaemia as significant risk factors for TAA. Conclusion AHSG concentrations distinguish plasma samples derived from TAA patients and controls. The findings of this study suggest that AHSG may be a potential biomarker for TAA that could lead to better diagnostic capabilities.
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spelling doaj.art-6ef15463af1840cf8391ce5d7f32660d2023-03-22T10:22:15ZengBMCBMC Cardiovascular Disorders1471-22612023-03-0123111510.1186/s12872-023-03154-6Tissue and plasma proteomic profiling indicates AHSG as a potential biomarker for ascending thoracic aortic aneurysmsRafailia Kazamia0Anna Keravnou1Areti Moushi2Kleitos Sokratous3Kyriaki Michailidou4Kristia Yiangou5Marinos Soteriou6Stavroulla Xenophontos7Marios A. Cariolou8Evy Bashiardes9Department of Cardiovascular Genetics and The Laboratory of Forensic Genetics, The Cyprus Institute of Neurology and GeneticsDepartment of Cardiovascular Genetics and The Laboratory of Forensic Genetics, The Cyprus Institute of Neurology and GeneticsDepartment of Cardiovascular Genetics and The Laboratory of Forensic Genetics, The Cyprus Institute of Neurology and GeneticsOMass TherapeuticsBiostatistics Unit, The Cyprus Institute of Neurology and GeneticsDepartment of Cancer Genetics, Therapeutics and Ultrastructural Pathology, The Cyprus Institute of Neurology and GeneticsDepartment of Cardiology and Cardiovascular Surgery, American Medical CentreDepartment of Cardiovascular Genetics and The Laboratory of Forensic Genetics, The Cyprus Institute of Neurology and GeneticsDepartment of Cardiovascular Genetics and The Laboratory of Forensic Genetics, The Cyprus Institute of Neurology and GeneticsDepartment of Cardiovascular Genetics and The Laboratory of Forensic Genetics, The Cyprus Institute of Neurology and GeneticsAbstract Background Thoracic Aortic Aneurysms (TAAs) develop asymptomatically and are characterized by dilatation of the aorta. This is considered a life-threatening vascular disorder due to the risk of aortic dissection and rupture. There is an urgent need to identify blood-borne biomarkers for the early detection of TAA. The goal of the present study was to identify potential protein biomarkers associated with TAAs, using proteomic analysis of aortic tissue and plasma samples. Methods Extracted proteins from 14 aneurysmal and 12 non-aneurysmal thoracic aortic tissue specimens as well as plasma samples from six TAA patients collected pre-and postoperatively and six healthy controls (HC), were analyzed by liquid chromatography-tandem mass spectrometry. Proteomic data were further processed and following filtering criteria, one protein was selected for verification and validation in a larger cohort of patients and controls using a targeted quantitative proteomic approach and enzyme-linked immunosorbent assay, respectively. Results A total of 1593 and 363 differentially expressed proteins were identified in tissue and plasma samples, respectively. Pathway enrichment analysis on the differentially expressed proteins revealed a number of dysregulated molecular pathways that might be implicated in aneurysm pathology including complement and coagulation cascades, focal adhesion, and extracellular matrix receptor interaction pathways. Alpha-2-HS glycoprotein (AHSG) was selected for further verification in 36 TAA and 21 HC plasma samples using targeted quantitative proteomic approach. The results showed a significantly decreased concentration of AHSG (p = 0.0002) in the preoperative plasma samples compared with HC samples. Further analyses using a larger validation dataset revealed that AHSG protein levels were significantly lower (p = 0.03) compared with HC. Logistic regression analysis on the validation dataset revealed males, advanced age, hypertension and hyperlipidaemia as significant risk factors for TAA. Conclusion AHSG concentrations distinguish plasma samples derived from TAA patients and controls. The findings of this study suggest that AHSG may be a potential biomarker for TAA that could lead to better diagnostic capabilities.https://doi.org/10.1186/s12872-023-03154-6Thoracic aortic aneurysmTAABiomarkersProteomicMass spectrometryAortic tissue
spellingShingle Rafailia Kazamia
Anna Keravnou
Areti Moushi
Kleitos Sokratous
Kyriaki Michailidou
Kristia Yiangou
Marinos Soteriou
Stavroulla Xenophontos
Marios A. Cariolou
Evy Bashiardes
Tissue and plasma proteomic profiling indicates AHSG as a potential biomarker for ascending thoracic aortic aneurysms
BMC Cardiovascular Disorders
Thoracic aortic aneurysm
TAA
Biomarkers
Proteomic
Mass spectrometry
Aortic tissue
title Tissue and plasma proteomic profiling indicates AHSG as a potential biomarker for ascending thoracic aortic aneurysms
title_full Tissue and plasma proteomic profiling indicates AHSG as a potential biomarker for ascending thoracic aortic aneurysms
title_fullStr Tissue and plasma proteomic profiling indicates AHSG as a potential biomarker for ascending thoracic aortic aneurysms
title_full_unstemmed Tissue and plasma proteomic profiling indicates AHSG as a potential biomarker for ascending thoracic aortic aneurysms
title_short Tissue and plasma proteomic profiling indicates AHSG as a potential biomarker for ascending thoracic aortic aneurysms
title_sort tissue and plasma proteomic profiling indicates ahsg as a potential biomarker for ascending thoracic aortic aneurysms
topic Thoracic aortic aneurysm
TAA
Biomarkers
Proteomic
Mass spectrometry
Aortic tissue
url https://doi.org/10.1186/s12872-023-03154-6
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