Cigarette smoke extract induces foam cell formation by impairing machinery involved in lipid droplet degradation

Pflugers Arch. 2023 Nov 1. doi: 10.1007/s00424-023-02870-4. Online ahead of print.ABSTRACTThe formation of foam cells, lipid-loaded macrophages, is the hallmark event of atherosclerosis. Since cigarette smoking is a risk factor for developing atherosclerosis, the current study investigated the effects of cigarette smoke extract (CSE) on different events like expressions of genes involved in lipid influx and efflux, lipophagy, etc., that play vital roles in foam cell formation. The accumulation of lipids after CSE treatment U937 macrophage cells was examined by staining lipids with specific dyes: Oil red O and BODIPY493/503. Results showed an accumulation of lipids in CSE-treated cells, confirming foam cell formation by CSE treatment. To decipher the mechanism, the levels of CD36, an ox-LDL receptor, and ABCA1, an exporter of lipids, were examined in CSE-treated and -untreated U937 cells by real-time PCR and immunofluorescence analysis. Consistent with lipid accumulation, an increased level of CD36 and a reduction in ABCA1 were observed in CSE-treated cells. Moreover, CSE treatment caused inhibition of lipophagy-mediated lipid degradation by blocking lipid droplets (LDs)-lysosome fusion and increasing the lysosomal pH. CSE also impaired mitochondrial lipid oxidation. Thus, the present study demonstrates that CSE treatment affects lipid homeostasis by altering its influx and efflux, lysosomal degradation, and mitochondrial utilization, leading to the formation of lipid-loaded f...
Source: Pflugers Archiv : European Journal of Physiology - Category: Physiology Authors: Source Type: research