Accumulation of LDL in Rat Arteries Is Associated With Activation of Tumor Necrosis Factor-α Expression

Autor: Gunilla Nordin Fredrikson, Jan Nilsson, Audrey Niemann-Jönsson, Stefan Jovinge, Paul Dimayuga, Federico Calara, Mikko P. S. Ares
Rok vydání: 2000
Předmět:
Lipopolysaccharides
Male
medicine.medical_specialty
Time Factors
Endothelium
Arteriosclerosis
medicine.medical_treatment
Probucol
Enzyme-Linked Immunosorbent Assay
Biology
Antioxidants
Muscle
Smooth
Vascular
Rats
Sprague-Dawley
chemistry.chemical_compound
Internal medicine
medicine.artery
Hyperlipidemia
medicine
Animals
Humans
RNA
Messenger
Aorta
Cells
Cultured
Apolipoproteins B
Reverse Transcriptase Polymerase Chain Reaction
Tumor Necrosis Factor-alpha
Vascular disease
Microcirculation
medicine.disease
Immunohistochemistry
Rats
Lipoproteins
LDL
Endocrinology
medicine.anatomical_structure
Cytokine
Gene Expression Regulation
chemistry
Low-density lipoprotein
lipids (amino acids
peptides
and proteins)
Tumor necrosis factor alpha
Endothelium
Vascular
Cardiology and Cardiovascular Medicine
Oxidation-Reduction
Injections
Intraperitoneal
medicine.drug
Zdroj: Arteriosclerosis, Thrombosis, and Vascular Biology. 20:2205-2211
ISSN: 1524-4636
1079-5642
DOI: 10.1161/01.atv.20.10.2205
Popis: Abstract —Activation of vascular inflammation in response to hyperlipidemia is believed to play an important role during the early stages of atherogenesis. We demonstrate here that exposure of cultured, rat aortic smooth muscle cells to low density lipoprotein (LDL) stimulated tumor necrosis factor-α (TNF-α) mRNA and protein expression. Oxidative modification of LDL resulted in a reduction of this stimulatory effect. To analyze whether a similar response also occurs in vivo, we used a recently developed model in which the effects of a rapid accumulation of human LDL in rat arteries can be studied. As previously reported, epitopes specific for human apolipoprotein B began to accumulate in the aorta within 2 to 6 hours after injection of 6 mg of human LDL. This was followed by expression of oxidized LDL–specific epitopes after 12 hours. There was no vascular expression of TNF-α at baseline or in phosphate-buffered saline–injected control rats. However, 24 hours after injection of native LDL, there was a marked induction of TNF-α mRNA and immunoreactivity in the aorta and other large arteries, whereas injection of oxidized LDL was without effect in this respect. Preincubation of LDL with the antioxidant probucol before injection markedly decreased the expression of TNF-α immunoreactivity. The present findings support the notion that LDL may activate arterial expression of TNF-α and suggest 1 possible mechanism for the inflammatory response in the early stages of atherosclerosis. The role of LDL oxidation in this process remains to be fully elucidated.
Databáze: OpenAIRE
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