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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...

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Autores principales: Sikora, Marta, Lewandowska, Izabela, Kupc, Małgorzata, Kubalska, Jolanta, Graban, Ałła, Marczak, Łukasz, Kaźmierski, Radosław, Jakubowski, Hieronim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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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.
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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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