Immune mechanisms in atherosclerosis, especially in diabetes type 2.
Immune mechanisms in atherosclerosis, especially in diabetes type 2.
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DOI：
10.3389/fendo.2013.00162
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发表时间：
2013-10-29
影响因子：
5.2
通讯作者：
Frostegård J
中科院分区：
文献类型：
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作者：
Frostegård J
动脉粥样硬化和随之而来的心血管疾病（CVD）是2型糖尿病的主要并发症。动脉粥样硬化是一种慢性炎症性疾病，涉及病变中存在的不同类型的免疫活性细胞。尽管炎症和免疫激活在2型糖尿病的动脉粥样硬化中可能更明显，但糖尿病患者和非糖尿病患者之间似乎没有任何重大差异。因此，在两组中，动脉粥样硬化相关的免疫激活涉及类似的因素。免疫激活的原因尚不清楚，存在不同的相互不排斥的可能性。氧化和/或酶修饰形式的低密度脂蛋白（OxLDL）和死细胞存在于动脉粥样硬化斑块中。OxLDL可能发挥作用，具有促炎和免疫刺激作用，因为它激活T细胞，并且在较高浓度下具有细胞毒性。OxLDL中的炎性磷脂与磷酸胆碱（PC）作为暴露的抗原之一有关。在小鼠研究中，针对PC的抗体（抗PC）具有抗动脉粥样硬化作用，并且抗PC与人类动脉粥样硬化和心血管疾病的发生呈负相关。细菌和病毒被认为是免疫激活的潜在原因，但很难找到支持这一假设的直接证据，人类的抗生素试验也是阴性或不确定的。热休克蛋白（HSP）可能是致动脉粥样硬化免疫反应的主要靶点之一。斑块破裂的更直接原因包括细胞因子如白细胞介素1β（IL-1β）、肿瘤坏死因子（TNF）以及脂质介质如白三烯。此外，在糖尿病中，高血糖和氧化应激似乎加速了动脉粥样硬化的发展，其机制之一可能是通过促进免疫反应。为了证明免疫反应是动脉粥样硬化和CVD的病因，需要进一步研究免疫调节治疗。
Atherosclerosis and ensuing cardiovascular disease (CVD) are major complications of diabetes type 2. Atherosclerosis is a chronic inflammatory condition involving immunocompetent cells of different types present in the lesions. Even though inflammation and immune activation may be more pronounced in atherosclerosis in diabetes type 2, there does not appear to be any major differences between diabetics and non-diabetics. Similar factors are thus implicated in atherosclerosis-associated immune activation in both groups. The cause of immune activation is not known and different mutually non-exclusive possibilities exist. Oxidized and/or enzymatically modified forms of low-density lipoprotein (OxLDL) and dead cells are present in atherosclerotic plaques. OxLDL could play a role, being pro-inflammatory and immunostimulatory as it activates T-cells and is cytotoxic at higher concentrations. Inflammatory phospholipids in OxLDL are implicated, with phosphorylcholine (PC) as one of the exposed antigens. Antibodies against PC (anti-PC) are anti-atherogenic in mouse studies, and anti-PC is negatively associated with development of atherosclerosis and CVD in humans. Bacteria and virus have been discussed as potential causes of immune activation, but it has been difficult to find direct evidence supporting this hypothesis, and antibiotic trials in humans have been negative or inconclusive. Heat shock proteins (HSP) could be one major target for atherogenic immune reactions. More direct causes of plaque rupture include cytokines such as interleukin 1β (IL-1β), tumor necrosis factor (TNF), and also lipid mediators as leukotrienes. In addition, in diabetes, hyperglycemia and oxidative stress appear to accelerate the development of atherosclerosis, one mechanism could be via promotion of immune reactions. To prove that immune reactions are causative of atherosclerosis and CVD, further studies with immune-modulatory treatments are needed.