RIPK1, MLKL are Potential Biomarkers for Large Artery Atherosclerotic Acute Ischemic Stroke

Background: This research aimed to investigate the connection between large artery atherosclerosis-associated acute ischemic stroke (LAA-AIS) and the key protein receptor-interacting serine-threonine kinase 1 (RIPK1), mixed lineage kinase domain-like protein (MLKL) of necroptosis. Methods: We enrolled 111 patients with LAA-AIS along with 111 age and gender-matched healthy controls. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum RIPK1 and MLKL levels. Spearman correlation analysis was used to explore the correlation between RIPK1, MLKL, and the severity of LAA-AIS. Plotted receiver operating characteristic (ROC) curves to evaluate the diagnostic valueof RIPK1 and MLKL in predicting LAA-AIS. The independent risk variables of LAA-AIS were investigated using binary logistic regression analysis. Results: The serum levels of RIPK1 [0.25 ng/ml (IQR, 0.20, 0.34) vs 0.19 ng/ml (IQR, 0.16, 0.21)] and MLKL [3.16 ng/ml (IQR, 1.93- 5.22) vs 2.16 (IQR, 1.56-3.27)] in LAA-AIS patients were significantly higher than controls. On admission, the correlation coefficients between MLKL and NIHSS, MKLK and mRS score were 0.467 ( P <0.001) and 0.430 ( P =0.001), respectively. There was a weak but positive correlation between MLKL and the volume of cerebral infarction under MRI ( Rs =0.286, P =0.002) and unstable carotid atherosclerotic plaque ( Rs =0.482, P =0.001). Adding RIPK1 and MLKL to the basic model including traditional risk factors related to LAA-AIS improved the area under curve （AUC） from 0.799 to 0.882. Regression analysis suggested MLKL (OR=4.858, 95% CI: 1.256-18.786, P =0.022) is an independent risk factor for LAA-AIS. Conclusion: Our study demonstrated thatserum levels of RIPK1 and MLKL may be associated with LAA -AIS.