Abstract: Objective To detect plasma levels of receptor-interacting protein kinase 1 (RIP1), RIP3 and mixed lineage kinase domain-like protein (MLKL) in patients with chronic heart failure and explore the expression pattern of programmed necrosis signaling pathway RIP1/RIP3-MLKL in the progression of heart failure. Methods The patients with chronic heart failure (NYHA class II-IV) admitted in our hospital between February, 2020 and March, 2021 were prospectively enrolled in this study, with 21 healthy volunteers as the control group. The enrolled patients included 20 with grade II, 33 with grade III, and 43 with grade IV cardiac function. Fasting venous blood was collected from all the participants for detecting plasma levels of RIP1, RIP3, and MLKL and protein expressions of RIP1/RIP3-MLKL pathway using enzyme-linked immunosorbent assay (ELISA) and Western blotting. The patients with grade IV cardiac function were followed up for 5 months to evaluate the clinical prognostic indicators. Results Compared with the healthy volunteers, the patients with grade II, III and IV cardiac function had significantly increased plasma levels of RIP1, RIP3, and MLKL (P<0.01), and their levels were significantly higher in grade III/IV patients than in those with grade II cardiac function (P<0.01); the plasma levels of RIP1 and MLKL were significantly higher in grade IV patients than in grade III patients (P<0.05). The results of Western blotting also showed increased expressions of the proteins in the RIP1/RIP3-MLKL pathway in patients with heart failure. Pearson correlation analysis suggested that in patients with heart failure, the expression levels of RIP1, RIP3, and MLKL were positively correlated with SCR, AST, LVEDD and NT-proBNP (P<0.05). Follow-up study of the patients with grade IV cardiac function showed that higher expression levels of RIP1/RIP3-MLKL were associated with a poorer prognosis of the patients. Conclusion The expressions of RIP1, RIP3 and MLKL are significantly upregulated in patients with heart failure in positive correlation with the severity of the disease condition, and the activation of the RIP1/RIP3-MLKL signaling pathway may contribute to the occurrence, development and prognosis of chronic heart failure.

Key words: chronic heart failure; receptor-interacting protein kinase 1; receptor-interacting protein kinase 3; mixed lineage kinase domain-like protein; programmed necrosis