Foam cell formation and cholesterol trafficking and metabolism disturbances in atherosclerosis

Publication date: Available online 25 July 2018Source: Cor et VasaAuthor(s): Alexandrina Volobueva, Dongwei Zhang, Andrey V. Grechko, Alexander N. OrekhovAbstractFoam cells are typical components of atherosclerotic plaques, where they actively participate in the intracellular cholesterol accumulation. Onset and further progression of atherosclerosis is tightly associated with foam cell formation. These cells can originate both from the circulating monocytes/macrophages and from the resident smooth muscular cells migrating to the growing lesion. Classically activated pro-inflammatory M1 macrophages play an important role in atherogenesis, while M2 macrophages have a protective role in plaque stabilization. Molecular mechanisms for VSMC transformation towards foam cells remains to be studied in detail. Lipid droplets filling the foam cells are generated from metabolized modified low-density lipoproteins (LDL). LDL serves as the main source or lipids, which penetrate the endothelium both via LDL-receptor-dependent and alternative ALK-1-regulated pathways. Under pathologic conditions, LDL can undergo modification, such as sialylation, oxidation, glycation or carbamylation, leading to its excessive uptake by macrophages infiltrating the subendothelial space. Modified LDL is recognized mainly by scavenger receptors, such as SR-A1, CD36, LOX-1, CD68, those expression is low under physiological conditions and can be upregulated via JNK, Wnt and NF-kB signaling. In foam cells LDL is d...

Source: Cor et Vasa - July 25, 2018 Category: Cardiology Source Type: research