Effect of Advanced Glycation End Product–Modified Albumin on Tissue Factor Expression by Monocytes

Autor: M. Amar, Françoise Bridey, Véronique Ollivier, Jacques Hakim, F. Khechai, D. de Prost
Rok vydání: 1997
Předmět:
Glycation End Products
Advanced
medicine.medical_specialty
Glycosylation
Lactams
Macrocyclic
Serum albumin
Serum Albumin
Human
medicine.disease_cause
Antioxidants
Monocytes
Thromboplastin
Diabetes Complications
chemistry.chemical_compound
Tissue factor
Glycation
Internal medicine
Benzoquinones
Humans
Thrombophilia
Medicine
RNA
Messenger
Enzyme Inhibitors
Phosphorylation
Serum Albumin
biology
Hydroxyl Radical
business.industry
Monocyte
Quinones
Albumin
Free Radical Scavengers
Protein-Tyrosine Kinases
Acetylcysteine
Enzyme Activation
Oxidative Stress
medicine.anatomical_structure
Endocrinology
Gene Expression Regulation
Rifabutin
chemistry
biology.protein
Advanced glycation end-product
Cardiology and Cardiovascular Medicine
business
Protein Processing
Post-Translational
Tyrosine kinase
Oxidative stress
Signal Transduction
Zdroj: Arteriosclerosis, Thrombosis, and Vascular Biology. 17:2885-2890
ISSN: 1524-4636
1079-5642
DOI: 10.1161/01.atv.17.11.2885
Popis: Abstract Diabetes is associated with a hypercoagulable state that contributes to macrovascular complications, including cardiovascular events. The glycation reaction, a consequence of chronic hyperglycemia, has also been implicated in the pathogenesis of diabetic complications. Glycated proteins have receptors on monocytes and generate reactive oxygen species that can regulate the expression of a number of genes. As abnormal monocyte expression of tissue factor (TF), the main initiator of the coagulation cascade, is responsible for thrombosis in a number of clinical settings, we studied the effect of glycated albumin on monocyte TF expression. Mononuclear cells were incubated with glycated albumin for 24 hours, and monocyte TF activity was measured with a plasma recalcification time assay; TF antigen was measured by ELISA and TF mRNA by RT-PCR. Glycated albumin induced blood monocyte expression of the procoagulant protein TF at the mRNA level. Oxidative stress appeared to be involved in this effect, as the antioxidant N -acetylcysteine diminished TF mRNA accumulation in stimulated monocytes. Hydroxyl radicals, which may be generated inside cells from H 2 O 2 via the Fenton reaction, also appeared to be involved in this effect, as hydroxyl radical scavengers downregulated TF activity and antigen levels (but not TF mRNA). Finally, the involvement of activated protein tyrosine kinase in the transmission of the signal from the membrane to the nucleus was suggested by the inhibitory effect of herbimycin A. These results point to a new mechanism for the hypercoagulability often described in diabetic patients and suggest that antioxidants or protein tyrosine kinase inhibitors might be of therapeutic value in this setting.
Databáze: OpenAIRE
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