ABSTRACT: Mechanical thrombectomy (MT) has improved disability outcomes after ischemic stroke (IS), mainly when the so-called modified first-pass effect (mFPE) is achieved. This study aims to explore the proteomic profiling of thrombi composition in those patients who achieved mFPE. A prospective study was conducted based on consecutive IS patients who underwent MT for proteomic analysis of the thrombi, comparing whether the mFPE was achieved or not. A qualitative and quantitative protein analysis was performed using LC-MS/MS for DDA and SWATH-MS analysis, respectively. Dysregulated proteins were considered when the range p-value <0.05, and a fold change >1.5 (upregulated) or <0.6 (downregulated). A total of 88 patients were included, with a median age of 75 years (±16) and 55.7% females (49 patients). mFPE was presented in 48.9% (43 patients), and showed better functional independence at 90 days (62.2% vs. 37.8%; p=0.02). Proteomic qualitative DDA analysis showed 9 dysregulated proteins, while quantitative SWATH-MS analysis found 79 dysregulated proteins, both for patients who achieved mFPE (ACTN1, ACTN4, ANXA1, HSP90AB1, HSP90B1, PPBP, HBA1, FLNA, TLN1, SCPEP1, LGALS1, ADAP1, ITGB3, and S100A9). The most relevant biological pathways involved were endothelial dysfunction, platelet dysfunction, atheromatosis, and inflammation. This proteomic study provides new insights into the biological complexity of IS, revealing distinct protein expression patterns, particularly in those who achieved the mFPE, and may serve as potential biomarkers for prognostication and therapeutic targeting.
Susana Bravo 