366 the Novel Spleen Tyrosin Kinase Inhibitor Fostamatinib Disodium Attenuates Inflammation and Atherogenesis in Low Density Lipoprotein Receptor Deficient Mice

Hilgendorf, Ingo; Remer, Imke; Eisele, S.; Zeschky, Katharina; Colberg, Christian; Hoppe, Natalie; Bode, Constantin; Zirlik, Andreas; Willecke, Florian

doi:10.1016/s1567-5688(11)70367-1

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“…Orally administered fostamatinib, a recently developed Syk inhibitor, reduced atherosclerosis in LDLR-deficient mice by as much as 58% (767). Both endothelial inflammation and monocyte migration were inhibited.…”

Section: Canonical Nf-b Signaling Through the Cbm Complexmentioning

confidence: 99%

Molecular Biology of Atherosclerosis

Hopkins

2013

Physiological Reviews

382

344

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At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-␣ and related family members leading to activation of NF-B; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world.

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Section: Canonical Nf-b Signaling Through the Cbm Complexmentioning

confidence: 99%