Crucial role of interferon-γ and stimulated macrophages in cardiovascular disease
Crucial role of interferon-γ and stimulated macrophages in cardiovascular disease
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DOI：
10.2174/157016106777698379
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发表时间：
2006-07-01
影响因子：
4.5
通讯作者：
Fuchs, Dietmar
中科院分区：
文献类型：
--
作者：
Schroecksnadel, Katharina;Frick, Barbara;Fuchs, Dietmar
炎症和免疫激活在动脉粥样硬化和心血管疾病的发病机制中起着至关重要的作用。因此，在患有血管疾病的患者中发现了炎症标志物，如纤维蛋白原、铁蛋白、C-反应蛋白或新喋呤，其与疾病的程度强烈相关并预测疾病进展。人单核细胞衍生的巨噬细胞和树突状细胞的新蝶呤形成由促炎性细胞因子干扰素-γ诱导，其由活化的T淋巴细胞释放。人巨噬细胞主要参与斑块形成，干扰素-γ和巨噬细胞在细胞介导的免疫应答中抗微生物和抗肿瘤防御的氧化应激的发展中也很重要。干扰素-γ还刺激吲哚胺-2，3-双加氧酶，其将色氨酸降解为犬尿氨酸。同样，巨噬细胞是执行这种酶反应的最重要的细胞类型，但其他细胞如树突状细胞、内皮细胞或成纤维细胞也可以有助于色氨酸的消耗。同样，在冠心病患者中报告了色氨酸降解增强，并发现与新蝶呤形成增强相关。在慢性疾病如心血管疾病中，干扰素-γ诱导的生化反应可能对宿主细胞产生有害后果。与其他促炎细胞因子一致，干扰素-γ是活性氧簇（ROS）形成和释放的最重要触发剂。慢性ROS产生导致抗氧化剂如维生素C和E以及谷胱甘肽的消耗，结果是氧化应激的发展。氧化应激在动脉粥样硬化形成和心血管疾病进展中起着重要作用，它也可能导致其他氧化敏感物质如B族维生素（如叶酸和1312）的不可逆氧化。它们是同型半胱氨酸-甲硫氨酸代谢中必不可少的辅因子。在包括冠心病在内的几种疾病中发现了中度高同型半胱氨酸血症和细胞免疫激活之间的关联。并且数据表明高同型半胱氨酸血症可作为免疫激活的结果而发展。同型半胱氨酸在血液中的积累被确定为心血管疾病的独立危险因素。同型半胱氨酸本身具有进一步增强氧化应激的能力。干扰素-γ在动脉粥样硬化的形成和发展中起着重要作用。心血管疾病的进展。抗炎和免疫抑制治疗（例如，使用非甾体抗炎药或他汀类药物）也可能有助于减缓干扰素-γ的不良反应。
Inflammation and immune activation are crucially involved in the pathogenesis of atherosclerosis and cardiovascular disease. Accordingly, markers of inflammation such as fibrinogen, ferritin, C-reactive protein or neopterin are found in patients with vascular diseases, correlating strongly with the extent of disease and predicting disease progression. Neopterin formation by human monocyte-derived macrophages and dendritic cells is induced by the pro-inflammatory cyrokine interferon-gamma, which is released by activated T-lymphocytes. Human macrophages are centrally involved in plaque formation, and interferon-gamma and macrophages are also of importance in the development of oxidative stress for antimicrobial and antitumoural defence within the cell-mediated immune response. Interferon-gamma also stimulates the enzyme indoleamine-2,3-dioxygenase, which degrades tryptophan to kynurenine. Again, macrophages are the most important cell type executing this enzyme reaction, but also other cells like dendritic cells, endothelial cells or fibroblasts can contribute to the depletion of tryptophan. Likewise, enhanced tryptophan degradation was reported in patients with coronary heart disease and was found to correlate with enhanced neopterin formation.In chronic diseases such as in cardiovascular disease, biochemical reactions induced by interferon-gamma may have detrimental consequences for host cells. In concert with other pro-inflammatory cytokines, interferon-gamma is the most important trigger for the formation and release of reactive oxygen species (ROS). Chronic ROS-production leads to the depletion of antioxidants like vitamin C and E and glutathione, with a consequence that oxidative stress develope. Oxidative stress plays a major role in the atherogenesis and progression of cardiovascular disease, and it may also account for the irreversible oxidation of other oxidation-sensitive substances like B-vitamins (e.g. folic acid and 1312). They are essential cofactors in homocysteine-methionine metabolism. Associations between moderate hyperhomocysteinaemia and cellular immune activation are found in several diseases including coronary heart disease., and data indicate that hyperhomocysteinaemia may develop as a consequence of immune activation. Homocysteine accumulation in the blood is established as an independent risk factor for cardiovascular disease. Homocysteine itself has the capacity to further enhance oxidative stress.Interferon-gamma appears to be a central player in atherogenesis and in the development and. progression of cardiovascular disease. Anti-inflammatory and immunosuppressive treatment (e.g. with non-steroidal anti-inflammatory drugs or statins) may among other consequences, also contribute to a slow-down of the adverse effects of interferon-gamma.