Devy Diallo, Antonino Nicoletti
S andrine Delbosc
Introduction In ischemic stroke, the lack of blood flow triggers local inflammation and vascular injury, which further promotes tissue remodeling and angiogenesis. The aim of the present study was to investigate whether biomarkers of inflammation, hemostasis, vascular injury, and tissue remodeling measured in the plasma of stroke patients could stratify stroke patients concerning their clinical outcome. Methods We included 153 patients consecutively admitted for ischemic stroke treated by thrombolysis with or without thrombectomy. Blood was sampled at admission and 21 biomarkers related to inflammation (MPO, Osteopontin, CCL2/MCP-1, Adiponectin, Resistin, CD40L), hemostasis (uPA/Urokinase, alpha 2-macroglobulin, Serpin C1/Antithrombin-III, Serpin E1/PAI-1, Kallikrein 6/Neurosin, CD40L), endothelium activation (VCAM-1, ICAM-1 , CD31/PECAM-1, CD40L, Neuropilin-1), and tissue remodeling (Osteopontin, MMP-2, MMP-3, MMP-9, MMP-13, Cathepsin S, Cystatin C, Neuropilin-1) were assayed by a quantitative Luminex multiplex technic. Results Patients with higher NIHSS at admission presented higher levels of the inflammatory biomarker MPO, the hemostasis biomarker uPA/Urokinase and the endothelial activation biomarker VCAM. Logistic regression analyses correlated levels of uPA/Urokinase to NIHSS at arrival (p=0.0037), suggesting the major role of hemostasis in initial stroke gravity mRS>1 at 3 months was correlated to higher levels of MPO, the endothelial activation biomarkers ICAM-1, VCAM-1 and the tissue remodeling biomarkers Osteopontin, Cathepsine S, and lower levels of MMP-13. Logistic regression analyses correlated mRS 0-1 at three months to levels of Cathepsine S (p=0.0201) and VCAM-1 (p=0.0048). The area under ROC curve of both biomarkers was 0.75. Symptomatic hemorrhagic transformation, defined according to ECASS-3 criteria, was correlated to MMP-9 (p=0.0382) Conclusions As expected, initial NIHSS was related to early hemostasis response. Importantly, initial inflammatory response, endothelial activation and tissue remodeling biomarkers significantly impact the three-month outcome and the hemorrhagic transformation
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