Publication
Title
Axitinib attenuates intraplaque angiogenesis, haemorrhages and plaque destabilization in mice
Author
Abstract
Aim: An increased density of intraplaque (IP) microvessels in ruptured versus nonruptured human plaques suggests that IP neovascularization has a major causative effect on plaque development and instability. Possibly, vascular endothelial growth factor (VEGF) or other angiogenic factors mediate IP microvessel growth and plaque destabilization. Because apolipoprotein deficient mice with a heterozygous mutation (C1039G + / -) in the fibrillin-1 gene (ApoE(-/-) Fbn1(C1039G +/-)) manifest substantial 1P neovascularization, they represent a unique tool to further investigate angiogenesis and its role in atherosclerosis. Here, we examined whether administration of axitinib (inhibitor of VEGF receptor -1,-2 and -3) inhibits IP neovascularization and stabilizes atherosclerotic plaques. Methods: ApoE(-/-)Fbn1(C1039G +/-) mice were fed a western diet (WD) for 20 weeks. After 14 weeks WD, mice received axitinib (35 mu g/g) or solvent i.p. 4 x/week for 6 weeks. Cardiac function was monitored to evaluate the effect of axitinib on atherosclerosis-driven complications such as myocardial infarction. Results: Axitinib significantly reduced IP neovascularization, with subsequent less prevalence of IP haemorrhages. The smooth muscle cell content doubled, whereas the amount of macrophages decreased. Overall cardiac function was improved in axitinib-treated animals. Moreover, the number of animals with myocardial infarction was decreased by 40%. Coronary plaque formation was observed in almost all control animals whereas treated animals showed a 30% reduction in the occurrence of coronary plaques. Conclusions: Inhibition of VEGF receptor signalling by axitinib attenuates intraplaque angiogenesis and plaque destabilization in mice.
Language
English
Source (journal)
Vascular pharmacology. - New York, N.Y.
Publication
New York, N.Y. : 2018
ISSN
1537-1891
DOI
10.1016/J.VPH.2017.10.004
Volume/pages
100 (2018) , p. 34-40
ISI
000423256400004
Pubmed ID
29079346
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
High-Frequency Ultrasound Imaging System Vevo 2100.
Modulation of glycolytic flux as a new approach for treatment of atherosclerosis and plaque stabilization: a multidisciplinary study (MOGLYNET).
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 06.03.2018
Last edited 09.10.2023
To cite this reference