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High-density lipoproteins prevent the oxidized low-density lipoprotein-induced epidermal [corrected] growth factor receptor activation and subsequent matrix metalloproteinase-2 upregulation
High-density lipoproteins prevent the oxidized low-density lipoprotein-induced epidermal [corrected] growth factor receptor activation and subsequent matrix metalloproteinase-2 upregulation
- Source :
- Arteriosclerosis, thrombosis, and vascular biology. 25(6)
- Publication Year :
- 2005
-
Abstract
- Objectives— The atherogenic oxidized low-density lipoprotein (oxLDL) induces the formation of carbonyl-protein adducts and activates the endothelial growth factor receptor (EGFR) signaling pathway, which is now regarded as a central element for signal transduction. We aimed to investigate whether and by which mechanism the anti-atherogenic high-density lipoprotein (HDL) prevents these effects of oxLDL. Methods and Results— In vascular cultured cells, HDL and apolipoprotein A-I inhibit oxLDL-induced EGFR activation and subsequent signaling by acting through 2 separate mechanisms. First, HDL, like the aldehyde scavenger dinitrophenyl hydrazine, prevented the formation of oxLDL-induced carbonyl–protein adducts and 4-hydroxynonenal (HNE)–EGFR adducts. Secondly, HDL enhanced the cellular antioxidant defenses by preventing (through a scavenger receptor class B-1 (SR-BI)–dependent mechanism) the increase of intracellular reactive oxygen species (ROS) and subsequent EGFR activation triggered by oxLDL or H 2 O 2 . A pharmacological approach suggests that this protective effect of HDL is independent of cellular glutathione level and glutathione peroxidase activity, but it requires catalase activity. Finally, we report that oxLDL upregulates both membrane type 1 (MT1)-matrix metalloproteinase-1 (MT1-MMP) and MMP-2 through an EGFR-dependent mechanism and that HDL inhibits these events. Conclusions— HDLs block in vitro oxLDL-induced EGFR signaling and subsequent MMP-2 activation by inhibiting carbonyl adducts formation and cellular oxidative stress. These effects of HDL may participate to reduce cell activation, excessive remodeling, and alteration of the vascular wall.
- Subjects :
- CD36 Antigens
medicine.medical_specialty
medicine.medical_treatment
Matrix Metalloproteinase Inhibitors
medicine.disease_cause
Muscle, Smooth, Vascular
Cell Line
Protein Carbonylation
Growth factor receptor
Internal medicine
medicine
Drug Interactions
Scavenger receptor
Central element
Aldehydes
Apolipoprotein A-I
Chemistry
Growth factor
Hydrogen Peroxide
Atherosclerosis
Catalase
Cell biology
Up-Regulation
ErbB Receptors
Lipoproteins, LDL
Oxidative Stress
Endocrinology
Matrix Metalloproteinase 2
lipids (amino acids, peptides, and proteins)
Signal transduction
Cardiology and Cardiovascular Medicine
Cell activation
Lipoproteins, HDL
Reactive Oxygen Species
Oxidative stress
Lipoprotein
Signal Transduction
Subjects
Details
- ISSN :
- 15244636
- Volume :
- 25
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Accession number :
- edsair.doi.dedup.....49a800d5b5f4924948122850f57e8d11