Relationship Between Plasma RIP3 And Acute Aortic Atherosclerotic Cerebral Infarction

Background and PurposeStroke is one of the leading causes of the medical burden all over the world.Atherosclerotic cerebral infarction is the most common type of cerebral infarction.Cerebrovascular occlusion and thrombosis are two main pathological factors of atherosclerotic cerebral infarction.RIP3(receptor-interacting serine-threonine protein kinase 3)is a key protein that regulates survival,apoptosis,and necrosis of cell.RIP3 may aggravate atherosclerotic lesions by promoting macrophage necrosis.RIP3 also influence platelet activation and blood clots.In addition,RIP3 is involved in post-infarction brain cell death by mediating cell necrosis,inducing mitochondrial dysfunction and disrupting energy metabolism.RIP3 may be a important molecule in the occurrence and development of major atherosclerotic cerebral infarction,and may be a hematologic marker to predict the progression and poor prognosis of stroke.Cerebral infarction is harmful,while the current diagnosis,treatment and prognosis methods of this disease are not very effective.This study aimed to explore the relationship between plasma RIP3 and acute aortic atherosclerotic cerebral infarction,as well as to provide some reference for the clinical diagnosis,treatment and prognosis of acute atherosclerotic cerebral infarction in a relatively convenient way with less damage to patients.MethodsThis prospective study enrolled 116 patients with acute cerebral infarction classified by TOAST as large aortic atherosclerotic type,40 healthy controls and 30 patients with acute cerebral infarction with small vessel occlusion.Fastening blood in the morning within 24 h from the onset was collected from all the patients.Plasma RIP3 levels were detected by RIP3 ELISA kit,and relevant data such as routine risk factors,important hematological indicators,infarction size and National Institute of Health Stroke Scale(NIHSS)score were recorded.Stroke progression was defined as any new neurological symptoms,signs,or NIHSS score increase of 2 points within 7 days after the onset of stroke.The poor prognosis was defined as a Modified Rankin Scale(MRS)score higher than 2 points 90 days after onset.Logistic regression model was used to evaluate the relationship between RIP3 and stroke progression and poor prognosis.The ROC curve was used to calculate the best predictive value for the disease progression and poor prognosis of patients with major atherosclerotic cerebral infarction.ResultsThe level of plasma RIP3 in patients with aortic atherosclerotic cerebral infarction was significantly higher than that in healthy controls(1067.0 pg/m L vs 706.9 pg/m L,p<0.05),and the level of plasma RIP3 was also significantly increased in patients with cerebral infarction with small vessel occlusion(1067.0pg/m L vs 815.9pg/m L,p<0.05).In patients with acute LAA type cerebral infarction,the level of plasma RIP3 in the poor prognostic group was significantly higher than that in the good prognostic group(1201.19pg/m L vs 932.92 pg/m L,p<0.05)).The level of plasma RIP3 in patients with stroke progression was significantly higher than that in patients without stroke progression(1186.53pg/m L vs 1032.54pg/m L,p<0.05).Patients in the highest plasma RIP3 quartile group were 11.39 times more likely to have stroke progression compared with patients in the lowest plasma RIP3 quartile(odds ratio,11.398;95%CI,2.071-62.736;P <0.05).Patients categorized in the highest quartile group of plasma RIP3 were also more likely to have poor outcomes at day 90(odds ratio,31.29;95% CI,4.69-208.78;P<0.05).According to the ROC curve,the optimal cut-off value of plasma RIP3 for predicting stroke progression in patients with acute LAA cerebral infarction was 1127.75pg/m L,with a specificity of 66.7% and a sensitivity of 69.2%.The optimal cut-off value of plasma RIP3 for predicting poor prognosis of LAA type cerebral infarction was 1181.82pg/m L,with a specificity of 89.7% and a sensitivity of 62.1%.ConclusionElevated plasma RIP3 was significantly associated with stroke progression and poor prognosis after 90 days in patients with major atherosclerotic cerebral infarction.Significant elevation of plasma RIP3 level was an independent risk factor for progression and poor prognosis of major atherosclerotic cerebral infarction stroke at 90 days.Significant increase in plasma RIP3 level can predict the progression and poor prognosis of atherosclerotic cerebral infarction.However,this needs to be verified by more multi-center,large sample studies.