Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-6822
Venalis, P; Maurer, B; Akhmetshina, A; Busch, N; Dees, C; Stürzl, M; Zwerina, J; Jüngel, A; Gay, S; Schett, G; Distler, O; Distler, J H W (2009). Lack of inhibititory effects of the anti-fibrotic drug imatinib on endothelial cell functions in vitro and in vivo. Journal of Cellular and Molecular Medicine, 13(10):4185-4191.
Systemic sclerosis (SSc) is a systemic autoimmune disease that is characterized by microangiopathy with progressive loss of capillaries and tissue fibrosis. Imatinib exerts potent anti-fibrotic effects and is currently evaluated in clinical trials. The aim of the present study was to exclude that the anti-fibrotic effects of imatinib are complicated by inhibitory effects on endothelial cell functions, which might augment vascular disease in SSc. Endothelial cells and mice were treated with pharmacologically relevant concentrations of imatinib. The expression of markers of vascular activation was assessed with real-time PCR. Proliferation was analyzed with the cell counting experiments and the MTT assay. Apoptosis was quantified with caspase 3 assays, annexin V in vitro and with TUNEL staining in vivo. Migration was studied with scratch and transwell assays. Tube forming was investigated with the matrigel assay. Imatinib did not alter the expression of markers of vascular activation. Imatinib did not increase the percentage of annexin V positive cells or the activity of caspase 3. No reduction in proliferation or metabolic activity of endothelial cells was observed. Imatinib did not affect migration of endothelial cells and did not reduce the formation of capillary tubes. Consistent with the in vitro data, no difference in the number of apoptotic endothelial cells was observed in vivo in mice treated with imatinib. Imatinib does not inhibit activation, viability, proliferation, migration or tube forming of endothelial cells in vitro and in vivo. Thus, treatment with imatinib might not augment further endothelial cell damage in SSc.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Center for Integrative Human Physiology|
04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||05 Dec 2008 10:56|
|Last Modified:||23 Nov 2012 14:18|
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