Imatinib treatment attenuates growth and inflammation of angiotensin II induced abdominal aortic aneurysm
2016 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 249, 101-109 p.Article in journal (Refereed) PublishedText
AbstractBackground Abdominal aortic aneurysm (AAA) is characterized by vascular remodeling with increased infiltration of inflammatory cells and apoptosis/modulation of vascular smooth muscle cells (SMCs). Imatinib is a selective inhibitor of several tyrosine kinases, including PDGF receptors, Abl, and c-kit. The objective of this study was to characterize the potential protective role of imatinib on AAA development and the molecular mechanisms involved. Methods Male ApoEâ/â mice were infused with angiotensin (Ang) II (1000Â ng/kg/min) for 4 weeks to induce AAA or saline as controls. Daily treatment with 10Â mg/kg imatinib, or tap water as control, was provided via gavage for 4 weeks. Results Treatment with imatinib was found to decrease the aortic diameter and vessel wall thickness, mediated by multiple effects. Imatinib treatment in AngII infused mice resulted in a reduced cellular infiltration of CD3Îµ positive T lymphocytes by 86% and reduced gene expression of mast cell chymase by 50% compared with AngII infused mice lacking imatinib. Gene expression analysis of SMC marker SM22Î± demonstrated an increase by 48% together with a more intact medial layer after treatment with imatinib as evaluated with SM22Î± immunostaining. Conclusion Present findings highlight the importance of tyrosine kinase pathways in the development of AAA. Our results show, that imatinib treatment inhibits essential mast cell, T lymphocyte and SMC mediated processes in experimental AAA. Thus, our results support the idea that tyrosine kinase inhibitors may be useful in the treatment of pathological vascular inflammation and remodeling in conditions like AAA.
Place, publisher, year, edition, pages
2016. Vol. 249, 101-109 p.
Abdominal aortic aneurysm, Vascular inflammation, Imatinib, Angiotensin II
Cell and Molecular Biology Physiology
IdentifiersURN: urn:nbn:se:liu:diva-127501DOI: 10.1016/j.atherosclerosis.2016.04.006ISI: 000376505800016PubMedID: 27085160OAI: oai:DiVA.org:liu-127501DiVA: diva2:924471