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Candidate plasma biomarkers for predicting ascending aortic aneurysm in bicuspid aortic valve disease

Candidate plasma biomarkers for predicting ascending aortic aneurysm in bicuspid aortic valve disease
Candidate plasma biomarkers for predicting ascending aortic aneurysm in bicuspid aortic valve disease
BACKGROUND: Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality affecting 1-2% of the population and is associated with a significantly increased risk of ascending aortic aneurysm. However, predicting which patients will develop aneurysms remains a challenge. This pilot study aimed to identify candidate plasma biomarkers for monitoring ascending aortic diameter and predicting risk of future aneurysm in BAV patients. METHODS: Plasma samples were collected pre-operatively from BAV patients undergoing aortic valve surgery. Maximum ascending aortic diameter was measured on pre-operative transoesophageal echocardiography. Maximum diameter ≥ 45 mm was classified as aneurysmal. Sequential Window Acquisition of all THeoretical Mass Spectra (SWATH-MS), an advanced mass spectrometry technique, was used to identify and quantify all proteins within the samples. Protein abundance and aortic diameter were correlated using logistic regression. Levene's test was used to identify proteins demonstrating low abundance variability in the aneurysmal patients (consistent expression in disease), and high variability in the non-aneurysmal patients (differential expression between 'at risk' and not 'at risk' patients). RESULTS: Fifteen plasma samples were collected (seven non-aneurysmal and 8 aneurysmal BAV patients). The mean age of the patients was 55.5 years and the majority were female (10/15, 67%). Four proteins (haemoglobin subunits alpha, beta and delta and mannan-binding lectin serine protease) correlated significantly with maximal ascending aortic diameter (p < 0.05, r = 0.5-0.6). Five plasma proteins demonstrated significantly lower variability in the aneurysmal group and may indicate increased risk of aneurysm in non-aneurysmal patients (DNA-dependent protein kinase catalytic subunit, lumican, tetranectin, gelsolin and cartilage acidic protein 1). A further 7 proteins were identified only in the aneurysmal group (matrin-3, glucose-6-phosphate isomerase, coactosin-like protein, peptidyl-prolyl cis-trans isomerase A, golgin subfamily B member 1, myeloperoxidase and 2'-deoxynucleoside 5'-phosphate N-hydrolase 1). CONCLUSIONS: This study is the first to identify candidate plasma biomarkers for predicting aortic diameter and risk of future aneurysm in BAV patients. It provides valuable pilot data and proof of principle that could be used to design a large-scale prospective investigation. Ultimately, a more affordable 'off-the-shelf' follow-on blood assay could then be developed in place of SWATH-MS, for use in the healthcare setting.
1749-8090
76
Harrison, Oliver
1feda5d5-8833-4587-9800-93135b68135a
Cagampang, Felino
7cf57d52-4a65-4554-8306-ed65226bc50e
Ohri, Sunil K.
8aa5698c-78cf-4f59-a5af-5afa46f0348c
Torrens, Christopher
15a35713-0651-4249-8227-5901e2cfcd22
Saliyyah, Kareem
38b4127c-3f52-43c4-b4c0-3ceddad04686
Modi, Amit
7655144c-358b-41c0-aa0b-514b3aa86a2a
Moorjani, Narain
21dc4371-f2f9-4a7a-ab94-f76abec7cad4
Whetton, Anthony D.
d2e48117-3dfc-4713-82dd-afc85bab739c
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Harrison, Oliver
1feda5d5-8833-4587-9800-93135b68135a
Cagampang, Felino
7cf57d52-4a65-4554-8306-ed65226bc50e
Ohri, Sunil K.
8aa5698c-78cf-4f59-a5af-5afa46f0348c
Torrens, Christopher
15a35713-0651-4249-8227-5901e2cfcd22
Saliyyah, Kareem
38b4127c-3f52-43c4-b4c0-3ceddad04686
Modi, Amit
7655144c-358b-41c0-aa0b-514b3aa86a2a
Moorjani, Narain
21dc4371-f2f9-4a7a-ab94-f76abec7cad4
Whetton, Anthony D.
d2e48117-3dfc-4713-82dd-afc85bab739c
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db

Harrison, Oliver, Cagampang, Felino, Ohri, Sunil K., Torrens, Christopher, Saliyyah, Kareem, Modi, Amit, Moorjani, Narain, Whetton, Anthony D. and Townsend, Paul A. (2018) Candidate plasma biomarkers for predicting ascending aortic aneurysm in bicuspid aortic valve disease. Journal of Cardiothoracic Surgery, 13 (1), 76. (doi:10.1186/s13019-018-0762-1).

Record type: Article

Abstract

BACKGROUND: Bicuspid aortic valve (BAV) disease is the most common congenital cardiac abnormality affecting 1-2% of the population and is associated with a significantly increased risk of ascending aortic aneurysm. However, predicting which patients will develop aneurysms remains a challenge. This pilot study aimed to identify candidate plasma biomarkers for monitoring ascending aortic diameter and predicting risk of future aneurysm in BAV patients. METHODS: Plasma samples were collected pre-operatively from BAV patients undergoing aortic valve surgery. Maximum ascending aortic diameter was measured on pre-operative transoesophageal echocardiography. Maximum diameter ≥ 45 mm was classified as aneurysmal. Sequential Window Acquisition of all THeoretical Mass Spectra (SWATH-MS), an advanced mass spectrometry technique, was used to identify and quantify all proteins within the samples. Protein abundance and aortic diameter were correlated using logistic regression. Levene's test was used to identify proteins demonstrating low abundance variability in the aneurysmal patients (consistent expression in disease), and high variability in the non-aneurysmal patients (differential expression between 'at risk' and not 'at risk' patients). RESULTS: Fifteen plasma samples were collected (seven non-aneurysmal and 8 aneurysmal BAV patients). The mean age of the patients was 55.5 years and the majority were female (10/15, 67%). Four proteins (haemoglobin subunits alpha, beta and delta and mannan-binding lectin serine protease) correlated significantly with maximal ascending aortic diameter (p < 0.05, r = 0.5-0.6). Five plasma proteins demonstrated significantly lower variability in the aneurysmal group and may indicate increased risk of aneurysm in non-aneurysmal patients (DNA-dependent protein kinase catalytic subunit, lumican, tetranectin, gelsolin and cartilage acidic protein 1). A further 7 proteins were identified only in the aneurysmal group (matrin-3, glucose-6-phosphate isomerase, coactosin-like protein, peptidyl-prolyl cis-trans isomerase A, golgin subfamily B member 1, myeloperoxidase and 2'-deoxynucleoside 5'-phosphate N-hydrolase 1). CONCLUSIONS: This study is the first to identify candidate plasma biomarkers for predicting aortic diameter and risk of future aneurysm in BAV patients. It provides valuable pilot data and proof of principle that could be used to design a large-scale prospective investigation. Ultimately, a more affordable 'off-the-shelf' follow-on blood assay could then be developed in place of SWATH-MS, for use in the healthcare setting.

Text
Harrison et al (2018) J Cardio Surg 13 76 - Version of Record
Available under License Creative Commons Attribution.
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Accepted/In Press date: 15 June 2018
e-pub ahead of print date: 22 June 2018

Identifiers

Local EPrints ID: 422116
URI: http://eprints.soton.ac.uk/id/eprint/422116
ISSN: 1749-8090
PURE UUID: 123631d4-070f-4ed0-90e5-2bd712d68b51
ORCID for Felino Cagampang: ORCID iD orcid.org/0000-0003-4404-9853

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Date deposited: 17 Jul 2018 16:30
Last modified: 22 Nov 2021 02:48

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Contributors

Author: Oliver Harrison
Author: Sunil K. Ohri
Author: Christopher Torrens
Author: Kareem Saliyyah
Author: Amit Modi
Author: Narain Moorjani
Author: Anthony D. Whetton
Author: Paul A. Townsend

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