| Autor: |
Sikora M; European Centre for Bioinformatics and Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, 60-965 Poznań, Poland. martas@ibch.poznan.pl., Lewandowska I; European Centre for Bioinformatics and Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, 60-965 Poznań, Poland. izek1988@gmail.com., Kupc M; Department of Biochemistry and Biotechnology, University of Life Sciences, 60-632 Poznań, Poland. gosia.kupc@gmail.com., Kubalska J; Department of Genetics, Institute of Psychiatry and Neurology, 02-957 Warsaw, Poland. kubalska@ipin.edu.pl., Graban A; First Department of Neurology, Institute of Psychiatry and Neurology, 02-957 Warsaw, Poland. graban@ipin.edu.pl., Marczak Ł; European Centre for Bioinformatics and Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, 60-965 Poznań, Poland. lukasmar@ibch.poznan.pl., Kaźmierski R; Department of Neurology and Cerebrovascular Disorders, Poznań University of Medical Sciences, L. Bierkowski Hospital, 60-631 Poznań, Poland. rkazmierski@ump.edu.pl., Jakubowski H; Department of Biochemistry and Biotechnology, University of Life Sciences, 60-632 Poznań, Poland. jakubows@rutgers.edu.; Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers-New Jersey Medical School, International Center for Public Health, Newark, NJ 07-103, USA. jakubows@rutgers.edu. |
| Abstrakt: |
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. |
