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RT Journal Article
SR Electronic
T1 Ischemic Stroke Thrombus Perviousness Is Associated with Distinguishable Proteomic Features and Susceptibility to ADAMTS13-Augmented Thrombolysis
JF American Journal of Neuroradiology
JO Am. J. Neuroradiol.
FD American Society of Neuroradiology
SP 22
OP 29
DO 10.3174/ajnr.A8069
VO 45
IS 1
A1 Schartz, Derrek
A1 Akkipeddi, Sajal Medha K.
A1 Rahmani, Redi
A1 Ellens, Nathaniel
A1 Houk, Clifton
A1 Kohli, Gurkirat Singh
A1 Worley, Logan
A1 Welle, Kevin
A1 Bhalla, Tarun
A1 Mattingly, Thomas
A1 Morrell, Craig
A1 Bender, Matthew T.
YR 2024
UL http://www.ajnr.org/content/45/1/22.abstract
AB BACKGROUND AND PURPOSE: Perviousness is the differential attenuation on CT of an intracranial arterial occlusive thrombus before and after IV contrast administration. While perviousness/permeability has been shown to be related to various clinical outcomes and reflects histopathologic composition, it remains unclear whether perviousness is also associated with differences in proteomic composition.MATERIALS AND METHODS: Retrieved clots from 59 patients were evaluated with quantitative mass spectrometry. Proteomic differences between high-perviousness (≥11 HU) and low-perviousness (&lt;11 HU) clots were investigated. Perviousness as a continuous variable was also correlated with protein abundance. Last, an ex vivo lysis assay was performed to investigate the differential susceptibility to tPA, deoxyribonuclease, and ADAMTS13 thrombolysis as a function of perviousness.RESULTS: In total, 2790 distinct proteins were identified. Thrombus perviousness was associated with distinct proteomic features, including depletion of the macrophage marker CD14 (P = .039, z = 1.176) and hemoglobin subunit ζ (P = .046, z = 1.68) in pervious clots. Additionally, proteins involved in platelet cytoskeleton remodeling (tropomyosin α-3-chain) and granule secretion/aggregation (synaptotagmin-like protein 4/FC region receptor II-a) were associated with increasing perviousness (P &lt; .006), among numerous other proteins. Monocyte/macrophage-associated proteins (apoptosis-associated specklike protein containing a CARD/SAMHD1) were also depleted in pervious emboli (P &lt; .002). Ex vivo lysis indicated that pervious clots were more susceptible to ADAMTS13-augmented tPA thrombolysis compared with impervious clots (P &lt; .05), though without differences in deoxyribonuclease digestion.CONCLUSIONS: Thrombus perviousness is associated with complex proteomic features, including differential abundance of platelet-related proteins in highly permeable clots with monocyte/macrophage depletion. This association may help to explain why highly pervious thrombi were also found more susceptible to ADAMTS13-augmented thrombolysis.CARDCaspase Recruitment DomainDNasedeoxyribonucleasedNTPasedeoxynucleoside triphosphohydrolaseFcγRIIAFC region receptor II-aFCfold changelog2FClog 2 fold changePYCARD/ASCapoptosis-associated specklike protein containing a CARDRBCred blood cellSYTL4synaptotagmin-like protein 4TPM3tropomyosin α-3 chainvWFvon Willebrand factorWBCwhite blood cell