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Abstract or Description
Chronic inflammation plays a critical role in the pathogenesis of atherosclerosis. At present, the mechanism(s) by which inflammation contributes to this disease isnot entirely understood. Inflammation is known to induce oxidative stress, of which one consequence is lipid peroxidation. This process leads to the production of malondialdehyde (MDA), which can subsequently break down to form acetaldehyde (AA). These two aldehyde by-products can covalently interact with the ε-amino group of lysineswithin proteins and lipoproteins leading to the formation of highly immunogenic malondialdehyde-acetaldehyde adducts (MAA-adducts). The aim of this study was to determine the in-vitro cytokine response of endothelial cells and macrophages treated with MAA-modified human serum albumin (HSA-MAA) and low-density lipoprotein (LDL-MAA). In addition, cells isolated from mice with exposure to MAA and high fat diets were stained and imaged for uptake of the modified macromolecules of interest. We found that exposure of endothelial cells resulted in increased expression of IL-6, TNF-α, ICAM-1, VCAM-1, and MCP-1 in response to incubation with HSA-MAA; whereas, the same treatment of macrophages resulted in increased expression of IL-6, TNF-α, and IL-1b. LDL-MAA incubationresulted in increased TNF-α expression in macrophages, but MCP-1 was elevated in endothelial cells. Interestingly, the quantitative and qualitative uptake of triglycerides was increased in both endothelial and macrophage cells when exposed to LDL-MAA compared to LDL alone. The results of these studies demonstrate that different MAA-adducts elicit unique responses in different cell types. Additionally, the presence of MAA appears to modulate the cells leading to increased uptake of triglycerides and further progression of the inflammatory response.
Opperman, Patrick J.; Duryee, Michael J.; Mikuls, Ted R.; Thiele, Geoffrey M.; Clemens, Dahn L.; and Anderson, Daniel R., "Malondialdehyde Acetaldehyde Adducts (MAA-Adducts) Direct Distinctive Pro-Inflammatory Responses in Endothelial and Macrophage Cell Lines" (2021). EMET Projects. 4.