Endoplasmic Reticulum Stress in Macrophages: The Vicious Circle of Lipid Accumulation and Pro-Inflammatory Response

Biomedicines

Ekaterina A. Ivanova¹  Mariam Bagheri Ekta²  Igor A. Sobenin²  Vasily N. Sukhorukov²  Victoria A. Khotina²  Alexander N. Orekhov² 

[1] Institute for Atherosclerosis Research, Skolkovo Innovative Center, 121609 Moscow, Russia;Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Research Institute of Human Morphology, 3 Tsyurupy Str., 117418 Moscow, Russia;

关键词: atherosclerosis;    endoplasmic reticulum stress;    macrophages;    pro-inflammatory response;    foam cells;   

DOI  :  10.3390/biomedicines8070210

来源: DOAJ

【 摘 要 】

The endoplasmic reticulum (ER) stress is an important event in the pathogenesis of different human disorders, including atherosclerosis. ER stress leads to disturbance of cellular homeostasis, apoptosis, and in the case of macrophages, to foam cell formation and pro-inflammatory cytokines production. In atherosclerosis, several cell types can be affected by ER stress, including endothelial cells, vascular smooth muscular cells, and macrophages. Modified low-density lipoproteins (LDL) and cytokines, in turn, can provoke ER stress through different processes. The signaling cascades involved in ER stress initiation are complex and linked to other cellular processes, such as lysosomal biogenesis and functioning, autophagy, mitochondrial homeostasis, and energy production. In this review, we discuss the underlying mechanisms of ER stress formation and the interplay of lipid accumulation and pro-inflammatory response. We will specifically focus on macrophages, which are the key players in maintaining chronic inflammatory milieu in atherosclerotic lesions, and also a major source of lipid-accumulating foam cells.

【 授权许可】

Unknown