TY - JOUR
T1 - Potential Biomarkers of Acute Ischemic Stroke Etiology Revealed by Mass Spectrometry-Based Proteomic Characterization of Formalin-Fixed Paraffin-Embedded Blood Clots
AU - Rossi, Rosanna
AU - Mereuta, Oana Madalina
AU - Barbachan e Silva, Mariel
AU - Molina Gil, Sara
AU - Douglas, Andrew
AU - Pandit, Abhay
AU - Gilvarry, Michael
AU - McCarthy, Ray
AU - O'Connell, Shane
AU - Tierney, Ciara
AU - Psychogios, Klearchos
AU - Tsivgoulis, Georgios
AU - Szikora, István
AU - Tatlisumak, Turgut
AU - Rentzos, Alexandros
AU - Thornton, John
AU - Ó Broin, Pilib
AU - Doyle, Karen M.
N1 - Publisher Copyright:
Copyright © 2022 Rossi, Mereuta, Barbachan e Silva, Molina Gil, Douglas, Pandit, Gilvarry, McCarthy, O'Connell, Tierney, Psychogios, Tsivgoulis, Szikora, Tatlisumak, Rentzos, Thornton, Ó Broin and Doyle.
PY - 2022/4/19
Y1 - 2022/4/19
N2 - Background and Aims: Besides the crucial role in the treatment of acute ischemic stroke (AIS), mechanical thrombectomy represents a unique opportunity for researchers to study the retrieved clots, with the possibility of unveiling biological patterns linked to stroke pathophysiology and etiology. We aimed to develop a shotgun proteomic approach to study and compare the proteome of formalin-fixed paraffin-embedded (FFPE) cardioembolic and large artery atherosclerotic (LAA) clots. Methods: We used 16 cardioembolic and 15 LAA FFPE thrombi from 31 AIS patients. The thrombus proteome was analyzed by label-free quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS). MaxQuant v1.5.2.8 and Perseus v.1.6.15.0 were used for bioinformatics analysis. Protein classes were identified using the PANTHER database and the STRING database was used to predict protein interactions. Results: We identified 1,581 protein groups as part of the AIS thrombus proteome. Fourteen significantly differentially abundant proteins across the two etiologies were identified. Four proteins involved in the ubiquitin-proteasome pathway, blood coagulation or plasminogen activating cascade were identified as significantly abundant in LAA clots. Ten proteins involved in the ubiquitin proteasome-pathway, cytoskeletal remodeling of platelets, platelet adhesion or blood coagulation were identified as significantly abundant in cardioembolic clots. Conclusion: Our results outlined a set of 14 proteins for a proof-of-principle characterization of cardioembolic and LAA FFPE clots, advancing the proteome profile of AIS human thrombi and understanding the pathophysiology of ischemic stroke.
AB - Background and Aims: Besides the crucial role in the treatment of acute ischemic stroke (AIS), mechanical thrombectomy represents a unique opportunity for researchers to study the retrieved clots, with the possibility of unveiling biological patterns linked to stroke pathophysiology and etiology. We aimed to develop a shotgun proteomic approach to study and compare the proteome of formalin-fixed paraffin-embedded (FFPE) cardioembolic and large artery atherosclerotic (LAA) clots. Methods: We used 16 cardioembolic and 15 LAA FFPE thrombi from 31 AIS patients. The thrombus proteome was analyzed by label-free quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS). MaxQuant v1.5.2.8 and Perseus v.1.6.15.0 were used for bioinformatics analysis. Protein classes were identified using the PANTHER database and the STRING database was used to predict protein interactions. Results: We identified 1,581 protein groups as part of the AIS thrombus proteome. Fourteen significantly differentially abundant proteins across the two etiologies were identified. Four proteins involved in the ubiquitin-proteasome pathway, blood coagulation or plasminogen activating cascade were identified as significantly abundant in LAA clots. Ten proteins involved in the ubiquitin proteasome-pathway, cytoskeletal remodeling of platelets, platelet adhesion or blood coagulation were identified as significantly abundant in cardioembolic clots. Conclusion: Our results outlined a set of 14 proteins for a proof-of-principle characterization of cardioembolic and LAA FFPE clots, advancing the proteome profile of AIS human thrombi and understanding the pathophysiology of ischemic stroke.
KW - FFPE proteomics
KW - biomarkers stroke etiology
KW - mass spectrometry proteomics
KW - stroke biomarkers
KW - thrombus proteome
UR - https://www.scopus.com/pages/publications/85129570931
U2 - 10.3389/fneur.2022.854846
DO - 10.3389/fneur.2022.854846
M3 - Article
VL - 13
JO - Frontiers in Neurology
JF - Frontiers in Neurology
M1 - 854846
ER -
