The Research On The Mechanism Of Sialic Acid And Lactadherin In The Inflammation Of Atherosclerosis

Part1 The clinical value of combination of serum total sialic acid, sialidase and high sensitive C reactive protein in patients with acute myocardial infarctionBackgroundAs a marker of acute inflammation, High sensitive C reactive protein (hs-CRP) is one of the independent risk factors of coronary heart disease (CHD) and hs-CRP was closely related to the infarct size and cardiac function of patients. Sialic acid is also a persistent inflammatory marker, and hs-CRP is a protein rich in SA. In acute inflammation, serum SA mainly come from acute phase protein decomposed by neuraminidase (NEU). So in the acute inflammation which caused by acute myocardial infarction (AMI), the content of total sialic acid (TSA) in the serum may be closely related to the content of hs-CRP.Objective(1) To compare the variation tendency of serum TSA and hs-CRP after myocardial infarction.(2) To Evaluate the clinical value of combined detection of serum TSA, hs-CRP and NEU in the diagnosis of acute myocardial infarction.(3) To Evaluate the relationship among serum TSA, hs-CRP, NEU and prognosis related indicators of infarction type, location, and hospital mortality.Methods(1) 98 healthy subjects (control group) and 105 AMI patients (AMI group) were selected as the study subjects;(2) AMI group was divided into 6 sub groups,6h group,1d group,3d group,5d group, 1w group and 2w group according to the serum sample collection time.(3) AMI group was divided into ST segment elevation myocardial infarction group (STEMI group) and non ST segment elevation myocardial infarction group (NSTEMI) according to the type of the myocardial infarction.(4) AMI group was divided into inferior wall infarction group and anterior wall infarction group according to the position of infarction.(5) AMI group was divided into death group and survival group according to whether death during hospitalization.(6) Used the enzyme analysis method to detect the level of serum TSA, used the immunoturbidimetry to detect the level of serum hs-CRP and used the ELISA method to detect the level of serum NEU.(7) Using statistical software SPSS22.0 to carry out statistical analysis.Results(1) Compared with the control group, the levels of TSA, hs-CRP and NEU in AMI group were significantly increased (U= 3742.5,798.5,8774.0 respectively, all P<0.001).(2) The overall trend of TSA and hs-CRP were similar, while NEU showed a slight upward trend.(3) Spearman correlation analysis showed that serum TSA and hs-CRP levels were significantly positively correlated (r=0.706, P<0.01) in AMI patients, and all time periods were significantly positively correlated (r=0.645,0.575,0.371,0.356,0.739, 0.766 respectively, all P<0.05).(4) Compared with the inferior wall infarction group, the serum TSA level and hs-CRP level in the anterior wall infarction group were significantly increased (U=3094.0,2965.5 respectively, all P<0.001). Compared with the survival group, the level of serum TSA and hs-CRP in the hospital death group were significantly increased (U=2829.0,3321.5 respectively, all P<0.001).(5) ROC curve area combined with hs-CRP and TSA in the diagnosis of AMI was 0.973 (P<0.001), the sensitivity was 87.9%, specificity was 98.6%.Conclusions(1) The overall trend of TSA and hs-CRP after myocardial infarction were similar, the content of serum TSA and hs-CRP level is closely related.(2) The combined detection of serum TSA, hs-CRP and NEU has a certain clinical value for the diagnosis of AMI.(3) The level of serum TSA and hs-CRP was related to the location of infarction and the death in hospital, which could provide reference for the clinical assessment of AMI severity and the risk of hospital mortality.Part2 The Clinical Value of Serum Total Sialic Acid and Lactadherin in the Coronary Heart DiseaseBackgroundBy promoting the removal of apoptotic cells, the lactadherin can reduce the inflammation. In this process, SA not only play a important role in the conformational change of lactadherin receptor integrin αυβ3 and αυβ5, but also change the function of lactadherin through the sialylation. Secondly, as a product of inflammation, SA is a long-term inflammatory marker in the circulation, which come from the acute phase reaction protein mainly. At present, the international generally accepted that coronary heart disease (CHD) is a chronic inflammatory disease, especially the role of inflammation in atherosclerotic (AS) plaque formation has received a wide attention. Therefore, to study the clinical value of SA and milk lectin in CHD, we can further understand the relationship between inflammation and the formation of atherosclerotic plaque.Objective(1) To study the relationship between serum TSA and lactadherin in the circulation.(2) To study the clinical value of combined TSA and lactadherin in the diagnosis of CHD and the assessment of the severity of CHD.(3) To study whether the serum TSA and lactadherin is a independent risk factors of CHD.Methods(1) Selected 78 cases of coronary angiography negative (control group) and 217 cases were diagnosed as CHD by coronary angiography (CHD group) as the research object.(2) The CHD group was divided into three subgroups as stable angina group (group StA), unstable angina group (group UA) and acute myocardial infarction group (group AMI).(3) Enzyme assay was used to detect the level of TSA, and the ELISA method was used to detect the level of lactadherin, and a fully automatic biochemical analyzer was used to detect the blood lipids and hs-CRP levels.(8) Using statistical software SPSS22.0 to carry out statistical analysis.Results(1) Compared with the control group, the patients with CHD have a higher level of serum TSA and a lower level of lactadherin (U/=4402.5、2736.0, P<0.001).(2) The AMI group has a higher level of serum TSA than the StA and UA groups (U=1329,957.5, P,0.001); the AMI group has a lower level of serum lactadherin than the StA groups (U=1517, P<0.001).(3) The spearman correlation analysis showed that the serum TSA has a positively correlation with the level of TG, hs-CRP and Gensini score, and has a negatively correlated with the level of lactadherin (P<0.01);the lactadherin has a negatively correlated with the level of TG, hs-CRP and Gensini score (P<0.01).(4) Logistic regression analysis showed that there was an independent correlation among the serum TSA, lactadherin and CHD (P<0.001).Conclusions(1) The serum TSA levels of CHD patients were increased, and the serum lactadherin content was lower, especially, the serum TSA level was the highest and the lactadherin level was lowest in the patients with AMI.(2) Serum TSA was negatively correlated with lactadherin.(3) With the higher level of serum TSA and the lower level of lactadherin, the stenosis degree of CHD was greater and the risk of CHD was higher.Part3 The Expression of Sialic Acid and Lactadherin on the atherosclerotic plaque in atherosclerotic mouse modelBackgroundDelaying the formation of AS and stabilizing the structure of AS is essential for prevention and treatment of coronary heart disease (CHD). In order to do this, we should deeply understand the structure of plaque deposits. Lipid and complex carbohydrates are the main deposits in the plaque. As a SA containing glycoprotein, lactadherin participated in the formation and development of AS. The study of the deposition characteristics of lactadherin in the plaque is of great significance for understanding the composition of the plaque and studying the treatment of lactadherin.Objective(1) To verify the effect of the combined treatment of male and female hormones on delaying the formation of atherosclerotic plaque.(2) To study the deposition characteristics of SA and lactadherin in atherosclerotic plaque of aortic valve and aorta.(3) To study the way of the sialylation of lactadherin in different parts of atherosclerotic plaques.Methods(1) Female mice were divided into 6 groups:wild type group, heterozygous group, control group, sham operation group, model group and treatment group. Except for the wild type and heterozygous group, the other groups were ApoE gene knockout mice;(2) Castration:mice in each group were underwent bilateral oophorectomy, sham operation group underwent the same operation without removal of the ovaries, only cut a piece of fat;Results(1) Compared with the control group, the weight of the wild type group and the heterozygous group were significantly increased (P<0.001), while the weight of the model group was significantly higher than that of the other 5 groups (P<0.01).(2) Compared with the control group, the total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) were significantly increased in the model group, while the high density lipoprotein cholesterol (HDL-C) levels decreased significantly (P<0.05). Compared with the model group, the levels of TC, TG and LDL-C in the treatment group were significantly lower, while the HDL-C level was significantly higher (P<0.05).(3) Oil red O results showed that the plaque of the model group was significantly increased, while the plaque was significantly decreased after treatment.(3) Lectin fluorescence showed that a large amount of α-2,6 SA was deposited in the plaque, and it increased in the model group and decreased in the treatment group, while the α-2,3 SA mainly expressed in the valve.(3) Immunofluorescence showed a large number of lactadherin was deposited in the plaque of the model group, while the treatment group was significantly decreased.(4) Double immunofluorescence display a-2,3 SA had no co-localization with lactadherin and a-2,6 SA had a significant co-localization with lactadherin in the plaque of the model group.Conclusions(1) The effect of combined treatment with estrogen and androgen on the formation of AS plaque was verified. It was found that the effect of combined treatment with estrogen and androgen in the treatment of aortic plaque was more significant.(2) In this study, we found a large number of S A and lactadherin were deposited in the atherosclerotic plaque, and the deposition of SA was mainly q-2,6 SA.(3) This study found that the deposition of lactadherin was mainly in α-2,6 sialylation, and in the process of AS plaque formation, lactadherin was mainly used for the removal of apoptotic cells.