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Serum Proteome Alterations in Human Cystathionine β-Synthase Deficiency and Ischemic Stroke Subtypes
Ischemic stroke induces brain injury via thrombotic or embolic mechanisms involving large or small vessels. Cystathionine β-synthase deficiency (CBS), an inborn error of metabolism, is associated with vascular thromboembolism, the major cause of morbidity and mortality in affected patients. Because...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627068/ https://www.ncbi.nlm.nih.gov/pubmed/31242583 http://dx.doi.org/10.3390/ijms20123096 |
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author | Sikora, Marta Lewandowska, Izabela Kupc, Małgorzata Kubalska, Jolanta Graban, Ałła Marczak, Łukasz Kaźmierski, Radosław Jakubowski, Hieronim |
author_facet | Sikora, Marta Lewandowska, Izabela Kupc, Małgorzata Kubalska, Jolanta Graban, Ałła Marczak, Łukasz Kaźmierski, Radosław Jakubowski, Hieronim |
author_sort | Sikora, Marta |
collection | PubMed |
description | Ischemic stroke induces brain injury via thrombotic or embolic mechanisms involving large or small vessels. Cystathionine β-synthase deficiency (CBS), an inborn error of metabolism, is associated with vascular thromboembolism, the major cause of morbidity and mortality in affected patients. Because thromboembolism involves the brain vasculature in these patients, we hypothesize that CBS deficiency and ischemic stroke have similar molecular phenotypes. We used label-free mass spectrometry for quantification of changes in serum proteomes in CBS-deficient patients (n = 10) and gender/age-matched unaffected controls (n = 14), as well as in patients with cardioembolic (n = 17), large-vessel (n = 26), or lacunar (n = 25) ischemic stroke subtype. In CBS-deficient patients, 40 differentially expressed serum proteins were identified, of which 18 were associated with elevated homocysteine (Hcy) and 22 were Hcy-independent. We also identified Hcy-independent differentially expressed serum proteins in ischemic stroke patients, some of which were unique to a specific subtype: 10 of 32 for cardioembolic vs. large-vessel, six of 33 for cardioembolic vs. lacunar, and six of 23 for large-vessel vs. lacunar. There were significant overlaps between proteins affected by CBS deficiency and ischemic stroke, particularly the cardioembolic subtype, similar to protein overlaps between ischemic stroke subtypes. Top molecular pathways affected by CBS deficiency and ischemic stroke subtypes included acute phase response signaling and coagulation system. Similar molecular networks centering on NFκB were affected by CBS deficiency and stroke subtypes. These findings suggest common mechanisms involved in the pathologies of CBS deficiency and ischemic stroke subtypes. |
format | Online Article Text |
id | pubmed-6627068 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66270682019-07-19 Serum Proteome Alterations in Human Cystathionine β-Synthase Deficiency and Ischemic Stroke Subtypes Sikora, Marta Lewandowska, Izabela Kupc, Małgorzata Kubalska, Jolanta Graban, Ałła Marczak, Łukasz Kaźmierski, Radosław Jakubowski, Hieronim Int J Mol Sci Article Ischemic stroke induces brain injury via thrombotic or embolic mechanisms involving large or small vessels. Cystathionine β-synthase deficiency (CBS), an inborn error of metabolism, is associated with vascular thromboembolism, the major cause of morbidity and mortality in affected patients. Because thromboembolism involves the brain vasculature in these patients, we hypothesize that CBS deficiency and ischemic stroke have similar molecular phenotypes. We used label-free mass spectrometry for quantification of changes in serum proteomes in CBS-deficient patients (n = 10) and gender/age-matched unaffected controls (n = 14), as well as in patients with cardioembolic (n = 17), large-vessel (n = 26), or lacunar (n = 25) ischemic stroke subtype. In CBS-deficient patients, 40 differentially expressed serum proteins were identified, of which 18 were associated with elevated homocysteine (Hcy) and 22 were Hcy-independent. We also identified Hcy-independent differentially expressed serum proteins in ischemic stroke patients, some of which were unique to a specific subtype: 10 of 32 for cardioembolic vs. large-vessel, six of 33 for cardioembolic vs. lacunar, and six of 23 for large-vessel vs. lacunar. There were significant overlaps between proteins affected by CBS deficiency and ischemic stroke, particularly the cardioembolic subtype, similar to protein overlaps between ischemic stroke subtypes. Top molecular pathways affected by CBS deficiency and ischemic stroke subtypes included acute phase response signaling and coagulation system. Similar molecular networks centering on NFκB were affected by CBS deficiency and stroke subtypes. These findings suggest common mechanisms involved in the pathologies of CBS deficiency and ischemic stroke subtypes. MDPI 2019-06-25 /pmc/articles/PMC6627068/ /pubmed/31242583 http://dx.doi.org/10.3390/ijms20123096 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sikora, Marta Lewandowska, Izabela Kupc, Małgorzata Kubalska, Jolanta Graban, Ałła Marczak, Łukasz Kaźmierski, Radosław Jakubowski, Hieronim Serum Proteome Alterations in Human Cystathionine β-Synthase Deficiency and Ischemic Stroke Subtypes |
title | Serum Proteome Alterations in Human Cystathionine β-Synthase Deficiency and Ischemic Stroke Subtypes |
title_full | Serum Proteome Alterations in Human Cystathionine β-Synthase Deficiency and Ischemic Stroke Subtypes |
title_fullStr | Serum Proteome Alterations in Human Cystathionine β-Synthase Deficiency and Ischemic Stroke Subtypes |
title_full_unstemmed | Serum Proteome Alterations in Human Cystathionine β-Synthase Deficiency and Ischemic Stroke Subtypes |
title_short | Serum Proteome Alterations in Human Cystathionine β-Synthase Deficiency and Ischemic Stroke Subtypes |
title_sort | serum proteome alterations in human cystathionine β-synthase deficiency and ischemic stroke subtypes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627068/ https://www.ncbi.nlm.nih.gov/pubmed/31242583 http://dx.doi.org/10.3390/ijms20123096 |
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