期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 68, 期 23, 页码 3933-3947出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-011-0688-4
关键词
Lipolysis; Small Rho GTPases; Adipose triglyceride lipase; Macrophages; Cytoskeleton; Atherosclerosis
资金
- Austrian Science Fund FWF [SFB-LIPOTOX F30, P19186, P22521]
- Austrian Federal Ministry of Science and Research
- Medical University of Graz
- Austrian Science Fund (FWF) [F 3004, F 3005, P 22521] Funding Source: researchfish
- Austrian Science Fund (FWF) [P19186] Funding Source: Austrian Science Fund (FWF)
Infiltration of monocytes and macrophages into the site of inflammation is critical in the progression of inflammatory diseases such as atherosclerosis. Cell migration is dependent on the continuous organization of the actin cytoskeleton, which is regulated by members of the small Rho GTPase family (RhoA, Cdc42, Rac) that are also important for the regulation of signal transduction pathways. We have recently reported on reduced plaque formation in an atherosclerotic mouse model transplanted with bone marrow from adipose triglyceride lipase-deficient (Atgl-/-) mice. Here we provide evidence that defective lipolysis in macrophages lacking ATGL, the major enzyme responsible for triacylglycerol hydrolysis, favors an anti-inflammatory M2-like macrophage phenotype. Our data implicate an as yet unrecognized principle that insufficient lipolysis influences macrophage polarization and actin polymerization, resulting in impaired macrophage migration. Sustained phosphorylation of focal adhesion kinase [due to inactivation of its phosphatase by elevated levels of reactive oxygen species (ROS)] results in defective Cdc42, Rac1 and RhoA activation and in increased and sustained activation of Rac2. Inhibition of ROS production restores the migratory capacity of Atgl-/- macrophages. Since monocyte and macrophage migration are a prerequisite for infiltrating the arterial wall, our results provide a molecular link between lipolysis and the development of atherosclerosis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据