TY - JOUR
TI - Potential Biomarkers of Acute Ischemic Stroke Etiology Revealed by Mass Spectrometry-Based Proteomic Characterization of Formalin-Fixed Paraffin-Embedded Blood Clots
AU - Rossi, R.
AU - Mereuta, O.M.
AU - Barbachan e Silva, M.
AU - Molina Gil, S.
AU - Douglas, A.
AU - Pandit, A.
AU - Gilvarry, M.
AU - McCarthy, R.
AU - O'Connell, S.
AU - Tierney, C.
AU - Psychogios, K.
AU - Tsivgoulis, G.
AU - Szikora, I.
AU - Tatlisumak, T.
AU - Rentzos, A.
AU - Thornton, J.
AU - Ó Broin, P.
AU - Doyle, K.M.
JO - Frontiers in Neurology
PY - 2022
VL - 13
TODO - null
SP - null
PB - Frontiers Media S.A
SN - null
TODO - 10.3389/fneur.2022.854846
TODO - null
TODO - 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. 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.
ER -