Abstract
Objective:
The activation of nuclear factor-κB (NF-κB) is a crucial step in the arterial wall's response to injury. The identification and characterization of the NF-κB essential modulator-binding domain (NBD) peptide, which can block the activation of the IκB kinase complex, have provided an opportunity to selectively abrogate the inflammation-induced activation of NF-κB. The aim of the present study was to evaluate the effect of the NBD peptide on neointimal formation.
Methods and results:
In the rat carotid artery balloon angioplasty model, local treatment with the NBD peptide (300 μg/site) significantly reduced the number of proliferating cells at day 7 (by 40%; P<0.01) and reduced injury-induced neointimal formation (by 50%; P<0.01) at day 14. These effects were associated with a significant reduction of NF-κB activation and monocyte chemotactic protein-1 expression in the carotid arteries of rats treated with the peptide. In addition, the NBD peptide (0.01 to 1 μmol/L) reduced rat smooth muscle cell proliferation, migration, and invasion in vitro. Similar results were observed in apolipoprotein E(-/-) mice in which the NBD peptide (150 μg/site) reduced wire-induced neointimal formation at day 28 (by 47%; P<0.01).
Conclusions:
The NBD peptide reduces neointimal formation and smooth muscle cell proliferation/migration, both effects associated with the inhibition of NF-κB activation.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Angioplasty, Balloon / adverse effects
-
Animals
-
Apolipoproteins E / deficiency
-
Apolipoproteins E / genetics
-
Apoptosis / drug effects
-
Carotid Artery Injuries / enzymology
-
Carotid Artery Injuries / etiology
-
Carotid Artery Injuries / pathology
-
Carotid Artery Injuries / prevention & control*
-
Cell Movement / drug effects
-
Cell Proliferation / drug effects
-
Cells, Cultured
-
Chemokine CCL2 / metabolism
-
Disease Models, Animal
-
Dose-Response Relationship, Drug
-
Enzyme Activation
-
Female
-
Hyperplasia
-
I-kappa B Kinase / antagonists & inhibitors*
-
I-kappa B Kinase / metabolism
-
Intracellular Signaling Peptides and Proteins / metabolism*
-
Male
-
Matrix Metalloproteinase 2 / metabolism
-
Matrix Metalloproteinase 9 / metabolism
-
Mice
-
Mice, Knockout
-
Myocytes, Smooth Muscle / drug effects*
-
Myocytes, Smooth Muscle / enzymology
-
Myocytes, Smooth Muscle / pathology
-
NF-kappa B / metabolism
-
Peptides / pharmacology*
-
Phosphorylation
-
Protein Kinase Inhibitors / pharmacology*
-
Rats
-
Rats, Wistar
-
Tunica Intima / drug effects*
-
Tunica Intima / enzymology
-
Tunica Intima / pathology
Substances
-
Apolipoproteins E
-
Ccl2 protein, rat
-
Chemokine CCL2
-
Ikbkg protein, rat
-
Intracellular Signaling Peptides and Proteins
-
NBD peptide, mouse
-
NEMO protein, mouse
-
NF-kappa B
-
Peptides
-
Protein Kinase Inhibitors
-
I-kappa B Kinase
-
Ikbkb protein, mouse
-
Matrix Metalloproteinase 2
-
Mmp2 protein, rat
-
Matrix Metalloproteinase 9