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Stimulation of Vascular Endothelial Cells Using Neutrophil Extracellular Traps in the Presence of Low-Density Lipoprotein
Published on: August 12, 2025
Modified low density lipoproteins decrease the activity and expression of lysosomal acid lipase in human endothelial
Constantina Heltianu1, Alexandra Robciuc, Gabriela Botez
1Institute of Cellular Biology and Pathology N. Simionescu, 8, B. P. Hasdeu Street, PO Box 14-35, 050568 Bucharest, Romania. ina.heltianu@icbp.ro
Cell Biochemistry and Biophysics
|April 19, 2011
Summary
Modified LDL, common in diabetes and atherosclerosis, reduces lysosomal acid lipase (LAL) expression in vascular cells. LXR signaling can restore LAL levels, suggesting a new therapeutic target for related diseases.
Area of Science:
- Biochemistry
- Cell Biology
- Cardiovascular Research
Background:
- Lysosomal acid lipase (LAL) regulates cellular cholesterol homeostasis.
- Deficiency in LAL is linked to various disease pathologies.
- Modified LDL (oxidized or glycated) is prevalent in atherosclerosis and diabetes.
Purpose of the Study:
- To investigate the impact of oxidized and glycated LDL on LAL activity and expression.
- To determine the effects in human vascular endothelial cells (EC) and smooth muscle cells (SMC).
- To explore the role of LXR and PPAR-gamma signaling pathways in mediating these effects.
Main Methods:
- Cultured human EC and SMC were exposed to native LDL (nLDL), oxidized LDL (oxLDL), glycated LDL (gLDL), or HODE.
- LAL activity and expression were measured.
- Cells were treated with LXR agonist (T0901317) or PPAR-gamma agonist (rosiglitazone).
Main Results:
- oxLDL and HODE significantly downregulated LAL activity and expression in EC.
- gLDL significantly downregulated LAL activity and expression in SMC.
- The LXR agonist T0901317 reversed the decreased LAL expression in modified LDL-exposed EC and gLDL-exposed SMC.
- PPAR-gamma agonist showed a limited effect.
Conclusions:
- Modified LDL downregulates LAL expression in human EC and SMC in a cell-specific manner.
- The LXR signaling pathway is involved in this downregulation.
- This study is the first to demonstrate that modified LDL affects LAL expression.
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