The interleukin-1ß modulator gevokizumab reduces neointimal proliferation and improves reendothelialization in a rat carotid denudation model.
Atherosclerosis
; 236(2): 277-85, 2014 Oct.
Article
in En
| MEDLINE
| ID: mdl-25108619
ABSTRACT
OBJECTIVE:
Excessive neointima formation often occurs after arterial injury. Interleukin-1ß (IL-1ß) is a potent pleiotropic cytokine that has been shown to regulate neointimal proliferation. We investigated the effects of the IL-1ß modulator gevokizumab in a rat carotid denudation model.METHODS:
Sprague-Dawley rats were subjected to balloon denudation of the right carotid artery and were then randomized to receive a single subcutaneous infusion immediately after balloon injury of saline (control group, n = 13) or gevokizumab (gevokizumab groups, n = 15 in each group 1, 10 and 50 mg/kg). We evaluated the treatment effects on carotid intima-media thickness (IMT) using ultrasonography, on endothelial regrowth using Evans Blue staining and on inflammatory response using histology. We also assessed the effects of IL-1ß and gevokizumab on human umbilical vein endothelial cells (HUVEC) and rat smooth muscle cells.RESULTS:
We found that carotid IMT, in the proximal part of the denuded artery at day 28, was decreased by gevokizumab 1 mg/kg compared with controls. Neointima area and the intima/media area ratio were both reduced in the gevokizumab 1 mg/kg-treated group. Gevokizumab at the 1 mg/kg dose also improved endothelial regrowth. No effect was observed with gevokizumab 10 or 50 mg/kg. Gevokizumab also decreased the inflammatory effect of IL-1ß in in vitro cell experiments and protected HUVECs from IL-1ß's deleterious effects on cell migration, apoptosis and proliferation.CONCLUSION:
A single administration of gevokizumab 1 mg/kg improves endothelial regrowth and reduces neointima formation in rats following carotid denudation, at least in part through its beneficial effects on endothelial cells.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carotid Artery Injuries
/
Neointima
/
Antibodies, Monoclonal, Humanized
Type of study:
Clinical_trials
Language:
En
Journal:
Atherosclerosis
Year:
2014
Document type:
Article
Affiliation country:
Canada