Περίληψη:
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.
Συγγραφείς:
Rossi, R.
Mereuta, O.M.
Barbachan e Silva, M.
Molina Gil, S.
Douglas, A.
Pandit, A.
Gilvarry, M.
McCarthy, R.
O'Connell, S.
Tierney, C.
Psychogios, K.
Tsivgoulis, G.
Szikora, I.
Tatlisumak, T.
Rentzos, A.
Thornton, J.
Ó Broin, P.
Doyle, K.M.
