Study On The Correlation Between Ceramide And Large Artery Atherosclerotic Stroke

Background:One of the most prevalent subtypes of ischemic stroke is large artery atherosclerotic（LAA）stroke,and brain atherosclerosis is a substantial risk factor for LAA cerebral infarction.AS is an inflammatory condition in which macrophages and various lipids（low density lipoprotein cholesterol,ceramide and Sphingosine-1-phosphate）build up and exacerbate pathogenic processes.Scholars are currently focused on the relationship between the sphingomyelin signaling pathway and the formation and progression of AS,with promising results.Ceramide（Cer）is at the core of sphingomyelin signaling pathways,and it can affect the occurrence and development of atherosclerosis by regulating lipid metabolism,inflammatory response and vascular endothelial function.A large number of studies have found that there are high levels of ceramide,sphingomyelin and glycosphingolipid in AS plaques.Numerous studies have established that the inhibition of the de novo ceramide biosynthesis can slow the progression of atherosclerosis effectively.Ceramides have been discovered to be independently associated with cardiovascular disorders such as coronary heart disease and myocardial infarction in the cardiovascu lar area,but there are comparatively few investigations on ceramides and cerebrovas cular diseases,particularly ischemic stroke.Ceramides’ link to AS and LAA cerebral infarctions is expected to give fresh light on ischemic stroke prevention and treatment.Purposes:To investigate the relationship between various ceramides and the progression of AS and LAA infarctions,we compared the levels of these ceramides in healthy,AS and LAA infarction patients,as well as their clinical features,imaging and lab results,in order to learn more about how to prevent and treat ischemic stroke.Methods:There were 20 patients in group LAA who had an acute large artery atherosclerotic stroke,and 20 patients in group AS who had cerebral atherosclerosis rather than an infarction.Both groups fulfilled the inclusion criteria and had their cerebral vascular systems examined（CTA and color doppler ultrasound）.According to the kind of atherosclerotic plaque,it can be classified as stable or unstable plaque,as well as mild stenosis,moderate stenosis,or severe stenosis,depending on the degree of vascular stenosis.The LAA group was classified into subgroups with mild and moderate-severe functional deficits using the NIHSS score standard questionnaire.Within 24 hours after being brought to the hospital,patients in groups AS and LAA had their fasting elbow venous blood drawn,and 16 patients in group LAA had their blood drawn again seven days later.Following centrifugation,the level of some particular ceramides（Cer（d18:1/16:0）,Cer（d18:1/18:0）,Cer（d18:1/20:0）,Cer（d18:1/20:1）,Cer（d18:1/22:0）,Cer（d18:1/22:1）,Cer（d18:1/24:0）,Cer（d18:1/24:1）,Cer（d18:1/26:0）,Cer（d18:1/26:1））in the serum was determined using LC-MS/MS.To explore the link between some specific ceramides and the occurrence and progression of AS and LAA cerebral infarction,researchers compared the levels of some specific ceramides,the NIHSS score,the state of vessels and relevant data in three groups.Results:1.Clinical data from patients in the control,AS and LAA groups: The average age,history of hypertension/diabetes/previous cerebral infarction,smoking/drinking history were all significantly higher in group LAA than in the control group（P < 0.05）.The average age,hypertension history/previous cerebral infarction history/drinking history ratio of patients in AS group were higher than those in control group（P<0.05）,TG level was higher than that in control group（P<0.05）,and HDL-C level was lower than that in control group（P<0.05）.The percentage of participants who had previously smoked was significantly higher in the LAA group than in the AS group（P< 0.05）.2.Ceramide levels in peripheral blood from patients in the control,AS and LAA groups: The AS group had significantly greater levels of Cer（d18:1/20:0）,Cer（d18:1/24:0）and total ceramide than the control group（P<0.05）.The AS group had a lower Cer（d18:1/16:0）/ Cer（d18:1/24:0）ratio than the control group（P<0.05）.Cer（d18: 1/18: 0）,Cer（d18: 1/20: 0）,Cer（d18: 1/C24: 0）,Cer（d18: 1/24: 1）and total ceramides in the LAA（within 24 hours of beginning）group were significantly higher than those in the control group（P<0.05）.Cer（d18:1/16:0）/Cer（d18:1/24:0）was significantly lower in the LAA（within 24 hours of beginning）group than in the control group（P<0.05）.3.Ceramide levels in peripheral blood of LAA patients change over time as the disease progresses: After seven days,the levels of various ceramides were reexamined in the peripheral blood of patients in group LAA.Cer（d18:1/16:0）,Cer（d18:1/18:0）,Cer（d18:1/20:0）,Cer（d18:1/20:1）and Cer（d18:1/22:1）levels were all significantly higher in patients 7 days after onset than in patients within 24 hours of onset（P<0.05）.4.subgroup analysis:（1）Plaque stability subgroup analysis: The levels of Cer（d18:1/18:0）,Cer（d18:1/20:0）,Cer（d18:1/22:0）,Cer（d18:1/24:1）,Cer（d18:1/26:0）,Cer（d18:1/26:1）in unstable plaque subgroup was significantly higher than that in stable plaque subgroup（P<0.05）.（2）subgroup study of the degree of vascular stenosis:Cer（d18:1/20:0）and Cer（d18:1/24:1）levels were considerably greater in the peripheral blood of patients with severe vascular stenosis than in the mild-moderate vascular stenosis subgroup（P<0.05）.（3）Neurological deficit subgroup analysis: The level of Cer（d18:1/16:0）in peripheral blood of patients with moderate-severe functional impairment subgroup was significantly higher than that in the mild functional impairment subgroup（P<0.05）.Conclusions:1.A variety of ceramides have been associated with atherosclerosis and LAAtype cerebral infarction.2.Cer（d18:1/20:0）and Cer（d18:1/24:1）in peripheral blood are correlated with atherosclerotic plaque stability and the severity of vascular stenosis.3.Cer（d18:1/16:0）levels in peripheral blood have been linked to the severity of LAA-type cerebral infarction.4.Cer（d18:1/18:0）and Cer（d18:1/20:0）in peripheral blood may serve as predictive index for the occurrence and progression of the LAA-type cerebral infarction.