The Investigation Of The Effects Of Specific Immune Responses To OxLDL On The Stability Of Atherosclerotic Plaque

Atherosclerosis(AS) is an inflammatory disease. Its atherosclerotic lesion contains large numbers of immune cells, particularly macrophages and T cells. Furthermore, AS is associated with systemic immune responses and signs of inflammation. More and more histopathological and clinical investigations point to activation of immune response as a cause of the instability of plaque and the occurrence of acute coronary syndromes. During recent years, experiments in gene-targeted mice have provided mechanistic evidence in support of the hypothesis that immune mechanisms are involved in atherosclerosis.Antibodies to oxLDL can be detected in atherosclerotic patients and experimental animals and are present in atherosclerotic lesions. These studies identified oxLDL as a candidate antigen in atherosclerosis. Further support for this notion came with the identification of cellular immune responses to oxLDL. T cells can be isolated from fresh human plaques, cloned, expanded in culture, and challenged with candidate antigens. By using this approach, oxLDL was shown to be a major autoantigen in the cellular immune response of atherosclerosis. Four of the 27 CD4+ T-cell clones isolated from human-8-atherosclerotic plaques recognized oxLDL in an HLA-DR-dependent manner.Some new studies have shown that patients with acute coronary syndromes (ACS) present elevated level of oxLDL and titer of antibody to oxLDL in their blood, and shown a positive relationsip with the severity of ACS. Another new study has shown that the proliferative response of T cells to oxLDL at high dose (10 g/ml) was significantly increased in 6 patients with unstable angina compared with 6 patients with stable angina. All these evidences indicate the specific immune responses to oxLDL may play an important role in the instability of plaque and the occurrence of ACS.The purpose of this research was to examine the activity of cellular immunology and the cellular immunological responses to oxLDL in patients with ACS, and to evaluate the immunological regulations of CRP and ASA by using methods of cytobiology and molecular immunology, so as to provide immunologic basis for the clinical prevention and treatment of ACS.Objective1. To investigate the effects of immune response on the stability of plaque.2. To investigate the effects of specific immune response to oxLDL, especially mediated by specific T cells on the stability of plaque.3. To investigate the effects of CRP, ASA on specific immune response to oxLDL in atherosclerosis.Subjects and methodsSubjectsA total of 84 subjects were recruited in the study, including 21 acute-9-myocardial infarction (AMI), 22 unstable angina pectoris (UAP), 20 stableangina pectoris (SAP) and 21 control subjects.Methods1. The proliferative responses of T cells were measured by MTS/PMS colorimetric assay.2. The percentage of activated T lymphocyte subsets and monocyte-macrophage were analyzed with flow cytometry.3. The level of autoantibodies against oxidized LDL was measured by indirective ELISA.4. the IFN-y concentration was measured by quantitative sandwich immunoassay.Results1. the relationship between immune response and ACS(1) Comparison of the proliferative response of T cells to PHA in different clinical groups showed: the proliferative response of T cells to PHA was significantly higher in AMI group(1.910.35) and UAP group(1.93.39) than in SAP group(1.45 0.31) and control group(1.43 ?0.27), (P<0.05); there was no significant difference between AMI group and UAP group, and no significant difference between SAP group and control group(P>0.05).(2) Comparison of the percentage of activated T lymphocyte subsets and monocyte-macrophage in different clinical groups showed: the percentages of activated T lymphocyte (CD3DR%), activated T lymphocyte subsets (CD4DR and CD8DR and activatedmonocyte-macrophage (CD14CD80) were significantly higher in AMI group and UAP group than in SA...