BMC Cardiovasc Disord. 2025 Dec 20. doi: 10.1186/s12872-025-05423-y. Online ahead of print.
ABSTRACT
BACKGROUND: Endothelial dysfunction is a key pathological mechanism in atherosclerotic cardiovascular disease, and methylglyoxal (MGO) has been identified as a major contributor to endothelial cell damage through its overabundance. In this study, the effects of MGO on atherosclerotic human endothelial cells were investigated.
METHOD: Human Umbilical Vein Endothelial cells (HUVECs) were first pre-treated with 1 mM palmitic acid (PA) for 24 h to induce lipotoxic conditions and then treated with 60 and 400 µM MGO for an additional 24 h. A total of six experimental groups were included: Control, 60 µM MGO, 400 µM MGO, PA, PA + 60 µM MGO, and PA + 400 µM MGO. Intracellular lipid accumulation was investigated using Oil-Red O staining. Apoptotic changes were assessed by flow cytometry, while nitric oxide (NO) levels were measured using the Griess assay. Gene expression patterns associated with angiogenesis, inflammation, lipoprotein, and cholesterol metabolism were investigated by real-time PCR.
RESULTS: Based on findings, the distribution of lipid droplets was detected exclusively in the PA-treated group, while no such accumulation was observed in the MGO (60 and 400 µM)-treated groups. Furthermore, co-treatment with PA-MGO (60 and 400 µM) significantly reduced apoptosis, while PA with 60 µM MGO elevated NO levels (p < 0.05). HUVECs' exposure to MGO remarkably upregulated levels of LPL, LPA, IL-8, and IFN-γ (p < 0.05), whereas IL-6 levels were elevated only in the PA-MGO group (p < 0.05). The PA-MGO combination significantly altered the expression of angiogenesis-related genes (p < 0.05).
CONCLUSIONS: MGO dose-dependently exacerbated the harmful effects of PA on HUVECs through increased inflammatory responses, impaired angiogenesis, and induction of nitrosative stress. Additionally, high concentrations of MGO altered the expression of genes related to lipid metabolism, including LPL and LP(a). Overall, the results indicate that MGO and PA may play a synergistic role in the occurrence of inflammation, lipid and angiogenesis disorders, and endothelial damage associated with CVDs.
PMID:41421984 | DOI:10.1186/s12872-025-05423-y