Research on participation of the immunity system in patient with coronary artery disease

不稳定型心绞痛(UA)患者外周血中淋巴细胞和单核细胞活化频率升高。冠状动脉痉挛在不稳定型心绞痛、急性心肌梗死等缺血性心脏病的发病机制中起重要作用。一氧化氮在冠状动脉痉挛中起重要作用。我们先前报道了冠状动脉痉挛型心绞痛(CSA)患者痉挛动脉中一氧化氮活性的缺乏。其他人报告说，一氧化氮影响免疫反应。因此，我们通过检测CsA患者外周血中产生干扰素(IFN)-γ和白介素4(IL)-4的T细胞的频率，研究了CsA患者Th1型和Th2型反应之间的平衡。采集了50例CsA患者、23例UA患者、36例稳定性心绞痛患者和21例胸痛综合征患者的外周血单个核细胞。经佛波醇酯和离子霉素刺激后，用三色流式细胞仪检测产生细胞因子的CD4+T细胞的数量。尿酸和环孢素A与产生干扰素-γ的CD4+T细胞的频率显著增加有关，而这些条件对产生IL-4的CD4+T细胞的频率没有显著的影响。最近，一氧化氮作为一种免疫调节剂改变Th1/Th2细胞因子产生的可能性已被证明。因此，我们研究了一氧化氮对CD4+T细胞产生细胞因子的影响。在刺激前用一氧化氮供体化合物培养24小时，可抑制产生干扰素-γ的CD4+T细胞频率的增加。我们证明CsA患者更倾向于Th1型反应，经NO处理后，T细胞表现出Th1型反应降低。

Patients with unstable angina (UA) show increased frequencies of lymphocyte and monocyte activation in the peripheral blood. Coronary artery spasm plays an important role in the pathogenesis of ischemic heart diseases such as UA and acute myocardial infarction. Nitric oxide plays an important role in coronary artery spasm. We previously reported a deficiency in the nitric oxide activity in the spasm arteries of patients with coronary spastic angina (CSA). Others have reported that nitric oxide influences the immune response. Therefore, we investigated the balance between Th1-type and Th2-type responses in patients with CSA by evaluating the frequencies of interferon (IFN)-gamma-producing T cells and interleukin (IL)-4-producing T cells in the peripheral blood of such patients.Peripheral blood mononuclear cells were collected from 50 consecutive patients with CSA, 23 consecutive patients with UA, 36 patients with stable angina, and 21 patients with chest pain syndrome. Cytokine-producing CD4+ T cells were quantified by 3-color flow cytometry after stimulation with phorbol myristate acetate and ionomycin. UA and CSA were associated with a significant increase in the frequency of CD4+ T cells producing IFN-gamma, whereas these conditions caused no significant difference in the frequency of CD4+ T cells producing IL-4. Recently, the potential for nitric oxide to act as an immunoregulator altering Th1/Th2 cytokine production has been demonstrated. Therefore, we investigated the effect of nitric oxide on cytokine production in CD4+ T cells. Culturing with a nitric oxide donor compound for 24 hours before stimulation, inhibited the increase in the frequency of CD4+ T cells producing IFN-gamma.We demonstrated that there was a preference towards the Th1-type response in patients with CSA and that T cells showed a reduced Th1-type response after treating them with NO.