Changes in plasma levels of RIPK1, RIPK3, and MLKL in patients with coronary atherosclerotic heart disease and its clinical predictive value.

Abstract

Coronary atherosclerotic heart disease (CHD) is caused by coronary atherosclerosis, which leads to stenosis and even occlusion of the lumen, resulting in myocardial ischemia, and necrosis subsequently. Its prevalence has been high for a long time. The prevention and treatment of CHD are important. The study aimed to investigate the role of plasma levels of receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), and mixed-lineage kinase domain-like protein (MLKL) in patients with CHD and its clinical predictive value. A total of 190 patients with CHD who were diagnosed by coronary angiography and 70 healthy subjects in cardiovascular department from September 2015 to May 2017 were enrolled in this study. Patients with CHD were assigned into 4 groups: Patients with stable angina pectoris (SAP, n=46), patients with unstable angina pectoris (UAP, n=56), patients with non-ST-segment elevation myocardial infarction (NSTEMI, n=42), and patients with ST-segment elevation myocardial infarction (STEMI, n=46). Patients with CHD were assigned into a single-vessel lesion group, a double-vessel lesion group, and a multi-vessel lesion group according to the results of coronary angiography, and the severity of coronary artery stenosis was determined by Gensini score. Plasma levels of RIPK1, RIPK3, and MLKL were measured by enzyme-linked immunosorbent assay (ELISA). The plasma levels of RIPK1, RIPK3, and MLKL in patients with CHD were significantly higher than those in the controls (P<0.05). The plasma levels of RIPK1, RIPK3, and MLKL in the UAP group were significantly higher than those in the SAP group (P<0.05). The plasma levels of RIPK1, RIPK3, and MLKL in NSTEMI and STEMI group were significantly higher than those in the UAP group (P<0.05). There was no significant difference between the NSTEMI group and STEMI group (P>0.05). The plasma levels of RIPK1, RIPK3 and MLKL were significantly increased with numbers of coronary artery lesions (P<0.05), which were positively correlated with Gensini scores. The multivariate logistic regression analysis showed that plasma levels of RIPK1, RIPK3, and MLKL were independent risk factors for severe coronary artery stenosis.The average period of follow-up was 24 months after hospital discharge. The patients were divided into 2 groups according to whether they had major adverse cardiovascular events (MACE). Compared with patient without MACE, patient with MACE had higher levels of RIPK1, RIPK3, and MLKL (P<0.05). Receiver operator characteristic (ROC) curve analysis showed that the area under curve of RIPK1 was 0.72 (P<0.001), the area under curve of RIPK3 was 0.83 (P<0.001), and the area under curve of MLKL was 0.75 (P<0.001). Plasma levels of RIPK1, RIPK3, and MLKL are closely related to CHD, and they have predictive value for the prognosis evaluation for patients with CHD.