Research On The Correiation Between Peripheral Blood T Lymphocyte Subgroup And The Severity Of Coronary Atherosclerosis

Background:Coronary heart disease is a huge threaten to human health and life since twentieth Century. However, its pathogenesis has not been fully elucidated, becoming a major obstacle in the treatment; studies on the pathogenesis, has been the hotspot in the internal medicine-cardiovascular department. Atherosclerosis is the pathological basis of cardiovascular and cerebrovascular disease lesions. In the process of its development,through fatty streaks, lipid plaque, fibrous plaque, plaque development period. In recent years clinical observation, coronary heart disease and end-stage with clinical manifestations of accelerating progress, manifested as sudden onset, risk degree higher characteristic. If treatment is not timely, mortality and disability rate increased significantly. Analysis of the pathological change found that vulnerable plaque is the main characteristic of the pathology, unstable plaque to rupture, the rapid development and caused the waterfall thrombosis, rapid and dramatic advances in disease cause. People once again aware of coronary heart disease and severe end-stage has the characteristics of evolution of acceleration, this kind of accelerated development stage at the end summarized for acute coronary syndrome. Coronary heart disease in the period of onset and progression of concealment, lethal and enter end-stage rate and disability rate increased significantly, constitute a great damage to people’s life and work. How early detection, early treatment and reduce its incidence and mutilation rate, is the focus of our attention.Atherosclerosis is characteristics by long process and end-stage progress rapidly. People found the pathogenesis of incidence have certain similar to trauma, tumor and inflammatory and autoimmune diseases, so the mechanism of pathogenesis and progression of atherosclerosis with various speculations; However, various theories in the occurrence and development of atherosclerosis in interpretation have encountered some difficulties, accurate to clarify the pathogenesis of atherosclerosis has become a research hotspot. Recently, people through the detection of activated immune cells and cytokines of patients with ACS and immune cell activation of AS in different periods of disease detection, detection of coronary heart disease patients with end-stage not only in plaque lesion can be detected large amounts of activated T lymphocytes and mononuclear cells, but also can be detected high levels of proinflammatory cytokines expression in peripheral blood. In the final stage of AS, enhancement of systemic inflammatory response performance, and according to the activation of T lymphocytes appear, so that people on the inflammation and immune to participate in disease, development become the focus of attention. The modified Gensini score of coronary artery by coronary angiography for coronary artery stenosis and the degree of stenosis integral, can objectively reflect the severity of coronary artery disease. Experiments show that, the disorder of the immune function may be involved in the acute myocardial infarction, directly or indirectly caused infarction extension or complications, detection of T lymphocyte subsets can reflect the immune function of patients. CD4+cells can help the humoral inmunity and cellular immunity function, it is through the secretion of cytokines and prompted B cells produce antibodies to play its immunological function. CD8+T cells divide into cytotoxic T cells and suppressor T cells, in which CD8+suppressor T cells, can suppress the humoral inmunity and cellular immunity function. They are mutual coordination, mutual restriction, participate in the regulation of the immune response together, They are in the changes of activity, number, proportion have some relationships with disease development and evolution. Only in the ratio of CD4+/CD8+is normal, can play the effect of normal, they are all together to maintain the balance of the immune system.Recent research shows that, CD4+CD28-T cells participate in the unstable plaque and acute coronary events. Compared with stable angina, acute coronary syndrome patients peripheral blood CD4+CD28-T cell subsets increased significantly Activate immune cells, thin fibrous hat, dissolution of collagen matrix and apoptosis of smooth muscle cells are associated with atherosclerotic plaque instability. The research discovered the CD4+CD28-T cell does not exist in the stable plaques, only exists in the unstable plaques, prompts the CD4+CD28-T cell and the plaques breakage has the direct relations. At present adjusts the CD4+CD28-T cell first to gather in they accurate mechanism of small stable mottling place related was still not explicit, The majority of T cell in artery heromatous plaque including CD4+CD28-T cell secretion IFN-y, the promotion macrophage splits up into other bubble cells and antigens presents the cell, activation other macrophage release matrix metalloproteinase (MMPs) and enzymes may cause the mottling to burst, simultaneously can increase the smooth muscle cell to express the MHC II kinds of members by Interferon-y (IFN-y) of CD4+CD28-T lymphocyte secretion, strengthens the inflammatory response process of atherosclerosis. In addition, IFN-y can suppress the fibroblast secretion collagen powerfully and suppresses the smooth muscle cell proliferation. Moreover the CD4+CD28-T lymphocyte has the function of direct dissolved endothelial cell and smooth muscle cell causes the mottling to burst. Interactions between these factors cause an increase in plaque instability, leading to plaque rupture.And the role of CD4+CD28-T cell subsets in contrast, CD4+CD25+Treg is a recent study found one of the regulatory T cell subsets. This kind of special T cell subgroup and balance between pathological effect nature T cells maintains own immune response stable state to take an important role at the organism. Humans mainly through regulatory t-cells, most notably CD4+CD25+Treg, immune to suppression of negative regulation of their reactive role of t-cells, reduce the incidence of autoimmune diseases, thereby maintaining immune tolerance. Sakaguchi finds removal of CD4+CD25+Treg mice can enter a serious multiorgan autoimmune disease. CD4+CD25+Treg may prevent to be born the latter3day excision thymus mouse to have the organ specificity own immune response.This indicated CD4+CD25+Treg is producing with the maintenance circumference own immunity tolerance aspect plays the prop role.Objective:This research plans through examination different clinical type CHD patient peripheral blood T cell subgroup proportion, for the purpose of discussion the relation of coronary heart disease patient peripheral blood T cell subgroup and the coronal atherosclerosis serious degree, we can provide the theoretical foundation for T-lymphocyte-mediated immune responses induction mottling progress.Methods:1. General Information:The57cases choosen in Department of Cardiology, Zhujiang Hospital, Southern Medical University from June,2012to December,2012. All selected patients with coronary angiography. Divides into4groups according to following standard:(1) Control group,13cases, have the chest pain medical history, has not discovered after physical examination, electrocardiogram and load test and cardiac ultrasound, CAG and other inspections unusually.(2) Stable angina pectoris (SAP) group,14cases, the tired angina pectoris outbreak nature in does not have the change in2months, the motion testing masculine gender, the CAG diagnosis is the coronary disease.(3) Unstable angina pectoris (UAP) group,15cases, diagnose for coronary disease and conform to the following condition:①Resting angina, duration>20min; Starts seriously the core colic or the worsening angina pectoris;②When angina pectoris outbreak, the electrocardiogram appears the short anemic ST section change, after the outbreak alleviation, the ST section change restores rapidly normal or close normal;③The cTnT negative, after the stem dies the angina pectoris to remove in outside.(4) Acute myocardial infarction (AMI) group,15cases, according to the clinical symptoms, the electrocardiogram change and dynamic evolution, the pure right room infarction excludes. The CAG diagnosis is the coronary disease.2. Selected exclusion criteria of patients with the following conditions:Merge apoplexy, serious hepatorenal function not entire; Before this6months have had the myocardial infarction; When in hospital the precordia ache surpasses for12hours; Removes the serious infectious disease, own immunity disease, as well as application inflammation suppression medicine like non-steroid body class anti-inflammatory agent, steroid and medicines and so on opium class.3. Coronarography evaluation criteria:All patients with coronary angiography, Judkins method is adopted, angiography by2experienced physician analysis is complete. Make the coronary artery radiography after the femoral artery or the radial artery, the narrow degree indicated by the diameter law, the coronary artery narrowly the main blood vessel≥50%as has the significance pathological change take the epicardium under.The coronary artery narrow<50%is a control group. With improving the Gensini standard, main left main coronary artery, left anterior descending and left circumflex branch, any one in the right coronary artery branch stenosis points:≤25%are1.0points,26%～49%is1.5points,50%is2.0points,51%～74%is3.0points,75%is4.0points,76%～89%is6.0points,90%is8.0points,91%～98%is12.0points,99%is16.0points,100%is32.0points. Various coronary artery branch grading coefficient according to this standard, coronary artery pathological change degree final integral sum of for each integral.4. Peripheral blood T lymphocyte subset examination:Flow cytometric detection of peripheral blood CD3+cell proportion of lymphocytes, CD4+, CD8+cell as a proportion of T lymphocytes, and the proportion of CD4+CD25+Treg and CD4+CD28-T cell as a proportion of CD4+T cells, calculate CD4+/CD8+ratios, and peripheral blood T lymphocyte subsets in correlation with the severity of coronary atherosclerosis.5. Statistical methods:All the statistics using SPSS16.0statistical software packages for processing. The measurement data indicated by the mean value±standard deviation (χ±s), comparison between multiple sets of single factor analysis of variance; if the variance does not align the Welch method, among the groups the multiple comparisons use the Dunnetts’T3examination. Count data with the χ2test. The relative analysis uses the Pearson method. Takes P<0.05to have statistical significance as the difference. Results:1. The baseline data:Among4groups of patients sex proportion, age distribution and patients with elevated blood pressure proportion, triglyceride (TG) and fasting plasma glucose (FPG) and other aspect comparisons, the difference does not have the statistical significance (all P>0.05). Serum total cholesterol (TC), uric acid (UA) in AMI group, compared with the other three groups there are significant statistical difference (P<0.05), there are no statistical differences between three groups (all P>0.05); Coronary Gensini score among the four groups compared to the presence of abnormal statistically significant differences (all P<0.01).2. The peripheral blood of patients in each group t lymphocyte subsets level and compare:2.1Various group of patient peripheral blood T lymphocyte subset levels:①The CD3+cells accounts for lymphocytes proportion in control group, SAP group, UAP group, and AMI group respectively is:(47.76±10.07)%,(56.61±7.49)%,(63.17±9.79)%,(70.17±10.59)%;②The CD4+cells accounts for CD3+cell proportion in control group, SAP group, UAP group and AMI group respectively is:(41.44±9.14)%,(52.49±9.60)%,(62.54±9.32)%,(68.28±11.32)%;③The CD8+cells accounts for CD3+cell proportion in control group, SAP group, UAP group and AMI group respectively is:(53.92±10.87)%,(44.66±9.86)%,(36.39±11.20)%,(31.10±9.54)%;④The CD4+CD25+cells accounts for CD4+cell proportion in control group, SAP group, UAP group and AMI group respectively is:(57.51±12.62)%,(50.19±9.27)%,(39.85±11.88)%,(32.37±9.56)%;⑤The CD4+CD28-cells proportion of CD4+cell proportion in control group, SAP group, UAP group, and AMI group respectively is:(12.61±9.06)%, (13.04±6.44)%,(20.68±9.50)%,(22.65±11.55)%;⑥The CD4+/CD8+ratio in control group, SAP group, UAP group and AMI group respectively is (0.81±0.27),(1.26±0.43),(2.03±1.27),(2.56±1.40)2.2Various group of patient peripheral blood T lymphocyte subset comparisons:Group multiple comparison know:①The CD3+cell accounts for the lymphocyte proportion, as well as CD4+and the CD8+cell accounts for the T lymphocyte proportion, three targets in the AMI group, the UAP group, the SAP group compare the control group to have the significance difference (P<0.05), in which CD4+, the CD8+cell proportion in the AMI group, the UAP group compares the SAP group and the control group has the extremely significance difference (P<0.01);②The CD4+CD25+Treg and the CD4+CD28-T cell accounts for the CD4+T cell total proportion in the AMI group and the UAP group compares the SAP group and the control group has the significance difference (P<0.05), But between the AMI group and the UAP group, as well as between the SAP group and the control group,they are not significance difference (all P>0.05).③The CD4+/CD8+ratio in the AMI group,and the UAP group compares the SAP group, and the control group has the significance difference (P<0.05), But between the AMI group and the UAP group, as well as between the SAP group and the control group,they are not significance difference (all P>0.05).Described above, immune response of T lymphocyte subsets of peripheral blood and mediated in coronary atherosclerotic plaque occurrence and development.3. The relative analysis of peripheral blood T lymphocyte subset proportion and Severity of coronary artery lesions(modified Gensini score):①the patient peripheral blood CD3+T cell and Gensini score show significant positive correlation (t=0.608,P<0.01);②the patient peripheral blood CD4+T cell and Gensini score show significant positive correlation (r=0.624, P<0.01);③the patient peripheral blood CD8+T cell and Gensini score show significant negative correlation (r=-0.548, P<0.01);④the patient peripheral blood CD4+CD25+Treg and Gensini score show significant negative correlation (r=-0.617, P<0.01);⑤the patient peripheral blood CD4+CD28-T cell and Gensini score show positive correlation, but correlational dependence not obviously (r=0.399, P<0.01);⑥the patient peripheral blood CD4+/CD8+and Gensini score show positive correlation, but correlational dependence not obviously (r=0.435, P<0.01)Conclusions:Peripheral blood T lymphocyte subsets involved in a wide range of coronary atherosclerosis development, the level and severity of coronary atherosclerosis is closely related to, the test is helpful to clinical diagnosis and prognosis prediction.