Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hilgendorf, I; Eisele, S; Remer, I; Schmitz, J; Zeschky, K; Colberg, C; Stachon, P; Wolf, D; Willecke, F; Buchner, M; Zirlik, K; Ortiz-Rodriguez, A; Lozhkin, A; Hoppe, N; von zur Muhlen, C; zur Hausen, A; Bode, C; Zirlik, A.
The oral spleen tyrosine kinase inhibitor fostamatinib attenuates inflammation and atherogenesis in low-density lipoprotein receptor-deficient mice.
ARTERIOSCL THROM VAS. 2011; 31(9): 1991-1999.
Doi: 10.1161/ATVBAHA.111.230847
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Zirlik Andreas
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Spleen tyrosine kinase (SYK) has come into focus as a potential therapeutic target in chronic inflammatory diseases, such as rheumatoid arthritis and asthma, as well as in B-cell lymphomas. SYK has also been involved in the signaling of immunoreceptors, cytokine receptors, and integrins. We therefore hypothesized that inhibition of SYK attenuates the inflammatory process underlying atherosclerosis and reduces plaque development. Low-density lipoprotein receptor-deficient mice consuming a high-cholesterol diet supplemented with 2 doses of the orally available SYK inhibitor fostamatinib for 16 weeks showed a dose-dependent reduction in atherosclerotic lesion size by up to 59±6% compared with the respective controls. Lesions of fostamatinib-treated animals contained fewer macrophages but more smooth muscle cells and collagen-characteristics associated with more stable plaques in humans. Mechanistically, fostamatinib attenuated adhesion and migration of inflammatory cells and limited macrophage survival. Furthermore, fostamatinib normalized high-cholesterol diet -induced monocytosis and inflammatory gene expression. We present the novel finding that the SYK inhibitor fostamatinib attenuates atherogenesis in mice. Our data identify SYK inhibition as a potentially fruitful antiinflammatory therapeutic strategy in atherosclerosis.
- Find related publications in this database (using NLM MeSH Indexing)
- Administration, Oral -
- Animals -
- Atherosclerosis - drug therapy
- Cell Differentiation - drug effects
- Cell Movement - drug effects
- Cholesterol, Dietary - administration & dosage
- Inflammation - drug therapy
- Intracellular Signaling Peptides and Proteins - antagonists & inhibitors
- Macrophages - drug effects
- Macrophages - physiology
- Mice -
- Oxazines - therapeutic use
- Protein-Tyrosine Kinases - antagonists & inhibitors
- Pyridines - therapeutic use
- Receptors, LDL - deficiency
- Syk Kinase -
- Find related publications in this database (Keywords)
- atherosclerosis
- macrophages
- signal transduction
- vascular biology
- SYK