Abstract 12: Targeted Deletion of I?B kinase ß Protects Mice from Obesity and Atherosclerosis
Vascular inflammation plays an essential role in the initiation and progression of atherosclerosis. IκB kinase β (IKKβ), a central coordinator of inflammatory responses through activation of NF-κB, has been implicated in vascular pathologies, but its cell-specific role in atherogenesis remains elusive. Here we show that IKKβ functions in smooth muscle cells to regulate vascular inflammatory responses and atherosclerosis development. Targeted deletion of IKKβ in smooth muscles cells protected LDL receptor-deficient mice from vascular inflammation and atherosclerosis induced by high-fat feeding. Unexpectedly, IKKβ-deficient mice were also protected against diet-induced obesity and associated metabolic disorders. Cell lineage analysis revealed that adipose mesenchymal stem cells express multiple smooth muscle cell markers. Ablation of IKKβ inhibited adipose stromal vascular cell differentiation, leading to a decreased number of mature adipocytes and an accumulation of adipocyte progenitor cells in the white adipose tissue. Furthermore, short hairpin RNA-mediated reduction of IKKβ expression or pharmacological inhibition of IKKβ activity in preadipocytes reduced the expression of adipogenic genes and diminished the ability of these cells to differentiate in vitro. These results demonstrate a pivot role of IKKβ in linking vascular inflammation with adipose development and atherosclerosis.
- © 2013 by American Heart Association, Inc.