Background and Purpose Acute ischemic stroke (AIS) thrombus perviousness/permeability has been shown to be related with various clinical outcomes and reflect histopathologic composition. However, it remains unclear if perviousness is also associated with differences in proteomic composition.
Materials and Methods Mechanical thrombectomy retrieved clots from 59 patients were evaluated with quantitative mass spectrometry. Proteomic differences between high perviousness (>11 Hounsfield Units; HU) and low perviousness (<11 HU) clots were investigated. Increasing perviousness as a continuous variable was also correlated with specific abundance across all identified proteins. Lastly, an ex vivo lysis assay was performed to investigate the differential susceptibility to tPA, DNase, ADAMTS13 thrombolysis as a function of perviousness.
Results From 85,244 distinct patients who had an MRI of the spine, 2,791 (3.3%) were identified with perineural cysts. Thrombus perviousness was negatively related to certain constituent proteins, including macrophage marker CD14 (P=0.039, Z=1.176), monocyte/macrophage associated proteins (PYCARD/ASC and SAMHD1) (P < 0.002), and hemoglobin subunit zeta (P=0.046, Z=1.68). A positive association between perviousness and other proteins was observed, including platelet cytoskeleton remodeling (TPM3) and platelet granule secretion/aggregation (SYTL4/FcγRIIA) (P < 0.006). Ex vivo lysis assay indicated that highly pervious clots were more susceptible to ADAMTS13-augmented tPA thrombolysis compared to low pervious clots (P < 0.05), though without differences to DNase digestion.
Conclusion Thrombus permeability is associated with distinguishable proteomics features, including greater abundance of platelet-related proteins in highly permeable clots and monocyte/macrophages in less permeable clots. These findings also suggest that highly pervious thrombi may be differentially susceptible to ADAMTS13 augmented thrombolysis.
Disclosures D. Schartz: None. S. Akkipeddi: None. N. Ellens: None. R. Rahmani: None. G. Kohli: None. R. Ismail: None. S. Chittaranjan: None. K. Welle: None. T. Bhalla: None. T. Mattingly: None. C. Morrell: None. M. Bender: None.
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