PT - JOURNAL ARTICLE AU - Schartz, Derrek AU - Akkipeddi, Sajal Medha K. AU - Rahmani, Redi AU - Ellens, Nathaniel AU - Houk, Clifton AU - Kohli, Gurkirat Singh AU - Worley, Logan AU - Welle, Kevin AU - Bhalla, Tarun AU - Mattingly, Thomas AU - Morrell, Craig AU - Bender, Matthew T. TI - Ischemic Stroke Thrombus Perviousness Is Associated with Distinguishable Proteomic Features and Susceptibility to ADAMTS13-Augmented Thrombolysis AID - 10.3174/ajnr.A8069 DP - 2024 Jan 01 TA - American Journal of Neuroradiology PG - 22--29 VI - 45 IP - 1 4099 - http://www.ajnr.org/content/45/1/22.short 4100 - http://www.ajnr.org/content/45/1/22.full SO - Am. J. Neuroradiol.2024 Jan 01; 45 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 (<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 < .006), among numerous other proteins. Monocyte/macrophage-associated proteins (apoptosis-associated specklike protein containing a CARD/SAMHD1) were also depleted in pervious emboli (P < .002). Ex vivo lysis indicated that pervious clots were more susceptible to ADAMTS13-augmented tPA thrombolysis compared with impervious clots (P < .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