Inflammation and Atherosclerosis
Inflammation and Atherosclerosis
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DOI：
10.1007/978-3-319-08798-6_13
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
E. Papadimitraki;D. Boumpas
中科院分区：
文献类型：
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作者：
E. Papadimitraki;D. Boumpas
动脉粥样硬化是一种进展缓慢的大中型动脉疾病，当动脉明显狭窄或斑块破裂时，会导致明显的疾病。炎症在动脉粥样硬化斑块的形成、发展和破裂中起着关键作用。先天免疫反应和获得性免疫反应在疾病发病机制中都具有重要作用。Toll样受体、NOD样受体和炎症小体是低密度脂蛋白和其他致动脉粥样硬化分子识别和内化以及随后与适应性免疫反应组件相互作用的关键组件。NLPR3炎症体通过激活caspase发挥作用，可由TLR激活启动，似乎在动脉粥样硬化和其他相关疾病如糖尿病、肥胖和代谢综合征中起着关键作用。然而，它的实验失活/修饰在该疾病的动物模型中提供了相互矛盾的结果。脂质紊乱也很重要，因为它们可以导致内皮细胞激活和炎症免疫反应的增强；即使是高密度脂蛋白也可能失去其动脉粥样硬化的保护能力。慢性炎症性疾病的特点是动脉粥样硬化加速：系统性红斑狼疮、类风湿性关节炎、干燥综合征和抗磷脂综合征患者表现出传统危险因素无法解释的心血管疾病发生率增加。通过整合动物模型、高通量技术和分子成像的数据来研究炎症。新出现的治疗方法以炎症为靶点，实现动脉粥样硬化的消退。胆固醇酯转移蛋白活性的调节剂和白细胞介素1抑制剂已经产生了令人振奋的结果。
Atherosclerosis is a slowly progressing disorder of large- and medium-sized arteries leading to overt disease when significant narrowing or atherosclerotic plaque rupture occurs. Inflammation plays a key role in atherosclerotic plaque formation, progression and rapture. Both innate and adaptive immune responses are important to disease pathogenesis. Toll-like receptors, NOD-like receptors and the inflammasome are key components of LDL and other atherogenic molecule recognition and internalization and the subsequent interaction with components of the adaptive immune response. The NLPR3 inflammasome acts through the activation of caspase, can be primed by TLR activation and seems to have a crucial role in atherosclerosis and other related disorders such as diabetes, obesity and the metabolic syndrome. However, its experimental inactivation/modification has provided conflicting results in animal models of the disease. Lipid perturbations are also important since they can lead to endothelial cell activation and the augmentation of the inflammatory immune response; even high density lipoproteins may lose their atheroprotective capacities. Chronic inflammatory diseases are characterized by accelerated atherosclerosis: Systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome and antiphospholipid syndrome patients display an increased incidence of cardiovascular disease not explained by traditional risk factors.Studying inflammation is achieved through integration of data from animal models, high-throughput technologies and molecular imaging. Emerging and novel therapies target inflammation to achieve atherosclerosis regression. Modulators of cholesteryl ester transfer protein activity and interleukin-1 inhibitors, have produced promising results.