A Study About The Correlation Between Different States Of Angiotensinogen And Atherosclerosis

BackgroundIt is widely accepted that rennin-angiotensin-aldosterone system plays an important role in development of vascular inflammation and promotes atherosclerosis.Angiotensinogen is the only precursor of the rennin-angiotensin-aldosterone system.However,there is no direct evidence suggested that angiotensinogen protein itself influences atherosclerosis.ObjectiveThe aim of this study was to determine whether measurements of Oxidized/Total AGT ratio could serve as a potential predictor for cardiovascular(CV)events in patients with atherosclerosis.Materials and methodsIn the first part study,a total of 144 participants including 68 patients with acute coronary syndrome and 76 individuals without atherosclerosis were included.In the second part study,a total of 82 participants including 39 patients with stable angina pectoris and 43 individuals without atherosclerosis were included in the study.Characteristics,including age,body mass index,smoke,total cholesterol,low-density lipoprotein(LDL),high-density lipoprotein(HDL)and creatinine,were compared between the groups.Human serum samples were collected and analyzed by ELISA for Total-AGT.And m-PEG western blot was used for detecting the levels of serum Reduced-AGT and Oxidized-AGT.ResultsIn the first part study,the concentration of Total-AGT in serum does not differ between acute coronary syndrome and control group(25.1±0.7ug/ml vs 23.8±1.1ug/ml;p=0.319).After stratified analysis by sex and smoking,no significant differences be found between the two groups(Male 25.1 ±0.7ug/ml vs 24.3±1.5ug/ml,p=0.613;Female 25.0±1.3ug/ml vs 22.8±1.4ug/ml,p=0.276.Smoking 26.5±1.Oug/ml vs 26.6±2.3ug/ml,p=0.965;No smoking 24.3±0.9ug/ml vs 23.0±1.lug/ml,p=0.362).And the ratio of Oxidized-AGT does not differ between acute coronary syndrome and control group(63.9±0.8%N=68;vs 62.09±0.8%N=76;p=0.104).Similarly,after stratified analysis by sex and smoking,no distinct differences be found between the two groups(Male 64.3 ±1.0%vs 62.7± 1.0,p=0.239;Female 63.2 ± 1.3%vs 61.3 ± 1.2%,p=0.288.Smoking 63.3±1.2%vs 60.6± 1.5%,p=0.160;No smoking 64.2± 1.0%vs 62.4±0.9%,p=0.185).Binary logistical regression show that the level of Total-AGT and the ratio of Oxidized-AGT both have no clear correlation with acute coronary syndrome(p=0.223,p=0.073).In the second part study,clinical details,demographic,and laboratory data of the patients with SAP(stable angina pectoris)and the control group are equivalent.The concentration of Total-AGT does not differ between the two groups(23.2±1.5ug/ml vs 19.7±1.7ug/ml;p=0.128).But the percentage of Oxidized-AGT is significantly increased in the patients with SAP(65.7±0.7%N=39)as compared to the control group(60.4±1.1%N=43;p=0.0002).In the meantime,binary logistical regression reveal that the ratio of Oxidized-AGT is positively correlated with SAP(P=0.001,OR>1).And the ROC curve for Oxidized-AGT show that AUC=0.710,cutoff point=67.88%.Then we backed to clinical patients to verify the result and observed that the proportion of patients with SAP is higher in the high ratio of Oxidized-AGT group than the low ratio of Oxidized-AGT group.This difference was statistically significant(p=0.001).ConclusionOur results indicate that though the level of Oxidized-AGT does not connect with ACS,it does positively be related to SAP.In acute stress conditions such as ACS,the body steady state is broken and each component inside may change a lot in a flash,but in such conditions like SAP,every aspect of the body is relatively stable,test results are more likely to reflect the real condition of atherosclerosis.So,the ratio of Oxidized-AGT may be used as a new target for predicting atherosclerosis.