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Background <p>Hyperglycemia and elevated saturated free fatty acids are key metabolic stressors implicated in vascular injury. However, the early transcriptional responses of endothelial cells to combined glucose and lipid stress remain incompletely defined. This exploratory in vitro study investigated whether high-glucose conditioning modifies palmitate-associated oxidative and endothelial stress-related gene expression responses in human umbilical vein endothelial cells (HUVECs).</p> Methods <p>HUVECs were cultured under low-glucose (LG; 1&#xa0;g/L) or high-glucose (HG; 4.5&#xa0;g/L) conditions and exposed to palmitic acid (Pal; 0.25, 0.5, or 1 mM) for 24&#xa0;h. Lipid peroxidation was assessed by measuring malondialdehyde (MDA) levels. The mRNA expression levels of endothelial stress-related and inflammatory markers, including EDN1/ET-1, NOS3/eNOS, VCAM1, SERPINE1/PAI-1, TNF, and IL6, were evaluated by RT-qPCR.</p> Results <p>Under LG conditions, Pal exposure increased MDA levels, particularly at 0.25 and 0.5 mM, whereas the HG condition showed a more complex non-linear lipid peroxidation response. In the HG environment, Pal exposure significantly increased ET-1 expression across all tested concentrations and significantly upregulated PAI-1 expression, while eNOS and VCAM-1 mRNA levels did not show significant changes. TNF-α showed a non-linear response, with induction at 0.5 mM Pal and suppression at 1 mM Pal, whereas IL-6 was mainly suppressed at higher Pal concentrations.</p> Conclusion <p>These findings suggest that high-glucose conditioning selectively modifies palmitate-associated endothelial stress-related transcriptional responses in HUVECs, particularly through ET-1 and PAI-1 upregulation. Because osmotic control, cell viability/cytotoxicity testing, protein-level validation, NO bioavailability assessment, and functional endothelial assays were not included, the results should be interpreted as exploratory transcriptional evidence of endothelial stress-associated remodeling rather than definitive proof of glucose-specific endothelial dysfunction.</p>

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Palmitate-associated ET-1 and PAI-1 transcriptional responses under high-glucose conditions in HUVECs: An exploratory glucolipotoxic stress model

  • 期刊论文

  • 发表日期：

    2026年7月10日

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  • Cem Abidoğlu,
  • Ebru Derici Eker,
  • Meral Urhan-Küçük

摘要

Background

Hyperglycemia and elevated saturated free fatty acids are key metabolic stressors implicated in vascular injury. However, the early transcriptional responses of endothelial cells to combined glucose and lipid stress remain incompletely defined. This exploratory in vitro study investigated whether high-glucose conditioning modifies palmitate-associated oxidative and endothelial stress-related gene expression responses in human umbilical vein endothelial cells (HUVECs).

Methods

HUVECs were cultured under low-glucose (LG; 1 g/L) or high-glucose (HG; 4.5 g/L) conditions and exposed to palmitic acid (Pal; 0.25, 0.5, or 1 mM) for 24 h. Lipid peroxidation was assessed by measuring malondialdehyde (MDA) levels. The mRNA expression levels of endothelial stress-related and inflammatory markers, including EDN1/ET-1, NOS3/eNOS, VCAM1, SERPINE1/PAI-1, TNF, and IL6, were evaluated by RT-qPCR.

Results

Under LG conditions, Pal exposure increased MDA levels, particularly at 0.25 and 0.5 mM, whereas the HG condition showed a more complex non-linear lipid peroxidation response. In the HG environment, Pal exposure significantly increased ET-1 expression across all tested concentrations and significantly upregulated PAI-1 expression, while eNOS and VCAM-1 mRNA levels did not show significant changes. TNF-α showed a non-linear response, with induction at 0.5 mM Pal and suppression at 1 mM Pal, whereas IL-6 was mainly suppressed at higher Pal concentrations.

Conclusion

These findings suggest that high-glucose conditioning selectively modifies palmitate-associated endothelial stress-related transcriptional responses in HUVECs, particularly through ET-1 and PAI-1 upregulation. Because osmotic control, cell viability/cytotoxicity testing, protein-level validation, NO bioavailability assessment, and functional endothelial assays were not included, the results should be interpreted as exploratory transcriptional evidence of endothelial stress-associated remodeling rather than definitive proof of glucose-specific endothelial dysfunction.