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Modulation of ERG25 expression by LDL in vascular cells
C Rodriguez1, B Raposo, J Martínez-González
1Cardiovascular Research Center, ICCC-CSIC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Cardiovascular Research
|April 2, 2003
Summary
Low density lipoproteins (LDL) downregulate ERG25, an enzyme in cholesterol biosynthesis, in vascular cells. Sterol regulatory element binding protein-2 (SREBP-2) is involved in this LDL-mediated regulation of ERG25 expression.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- Atherosclerosis Pathogenesis
Background:
- Plasma low density lipoproteins (LDL) are critical in atherosclerosis development.
- LDL alter gene expression in vascular cells, disrupting vessel wall function.
Purpose of the Study:
- To investigate the role of C-4 sterol methyl oxidase gene (ERG25) in vascular cells.
- To analyze the regulation of ERG25 by LDL and its underlying mechanisms.
Main Methods:
- Quantitative RT-PCR evaluated ERG25, sterol regulatory element binding protein (SREBP)-1, and SREBP-2 expression in porcine and human vascular cells and swine models.
- Western blot and electrophoretic mobility shift assay (EMSA) assessed SREBP-1 protein levels and DNA binding.
- SREBP-2 was overexpressed via transient transfection.
Main Results:
- ERG25 is expressed in vascular endothelial and smooth muscle cells and downregulated by LDL in a time- and dose-dependent manner.
- LDL-induced ERG25 downregulation was linked to SREBP catabolism and specifically affected SREBP-2 mRNA levels.
- ERG25 and SREBP-2 gene expression were reduced in hypercholesterolemic swine, and SREBP-2 overexpression inhibited LDL-mediated ERG25 downregulation.
Conclusions:
- LDL modulate ERG25 expression within the vascular wall.
- Sterol regulatory element binding protein-2 (SREBP-2) plays a significant role in the mechanism of LDL-mediated ERG25 regulation.