Orekhov Alexander N, Nikiforov Nikita N, Ivanova Ekaterina A, Sobenin Igor A
Laboratory for Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia.
Laboratory of Infection Pathology and Molecular Microecology, Institute of Human Morphology, 117418 Moscow, Russia.
J Clin Med. 2020 Apr 1;9(4):978. doi: 10.3390/jcm9040978.
Chronification of inflammation is the process that lies at the basis of several human diseases that make up to 80% of morbidity and mortality worldwide. It can also explain a great deal of processes related to aging. Atherosclerosis is an example of the most important chronic inflammatory pathology in terms of public health impact. Atherogenesis is based on the inflammatory response of the innate immunity arising locally or focally. The main trigger for this response appears to be modified low-density lipoprotein (LDL), although other factors may also play a role. With the quick resolution of inflammation, atherosclerotic changes in the arterial wall do not occur. However, a violation of the innate immunity response can lead to chronification of local inflammation and, as a result, to atherosclerotic lesion formation. In this review, we discuss possible mechanisms of the impaired immune response with a special focus on mitochondrial dysfunction. Some mitochondrial dysfunctions may be due to mutations in mitochondrial DNA. Several mitochondrial DNA mutations leading to defective mitophagy have been identified. The regulatory role of mitophagy in the immune response has been shown in recent studies. We suggest that defective mitophagy promoted by mutations in mitochondrial DNA can cause innate immunity disorders leading to chronification of inflammation.
炎症慢性化是构成全球80%发病率和死亡率的几种人类疾病的基础过程。它也能解释许多与衰老相关的过程。就公共卫生影响而言，动脉粥样硬化是最重要的慢性炎症性病理的一个例子。动脉粥样硬化的发生基于局部或局灶性产生的固有免疫的炎症反应。这种反应的主要触发因素似乎是修饰的低密度脂蛋白（LDL），尽管其他因素也可能起作用。随着炎症的迅速消退，动脉壁不会发生动脉粥样硬化改变。然而，固有免疫反应的破坏会导致局部炎症慢性化，进而导致动脉粥样硬化病变形成。在这篇综述中，我们讨论免疫反应受损的可能机制，特别关注线粒体功能障碍。一些线粒体功能障碍可能是由于线粒体DNA突变。已经鉴定出几种导致有缺陷的线粒体自噬的线粒体DNA突变。最近的研究表明了线粒体自噬在免疫反应中的调节作用。我们认为，线粒体DNA突变促进的有缺陷的线粒体自噬可导致固有免疫紊乱，从而导致炎症慢性化。
