Nov 17, 2019

Non-activatable mutant of inhibitor of kappa B kinase α (IKKα) exerts vascular site-specific effects on atherosclerosis in Apoe-deficient mice

Atherosclerosis
Pathricia V TilstamHeidi Noels

Abstract

IKKα is an important regulator of gene expression. As IKKα kinase inactivity in bone marrow-derived cells does not affect atherosclerosis, we here investigate the impact of a whole body-IKKα kinase inactivity on atherosclerosis. Apolipoprotein E (Apoe)-deficient mice homozygous for an activation-resistant Ikkα-mutant (IkkαAA/AAApoe-/-) and Ikkα+/+Apoe-/- controls received a Western-type diet. Atherosclerotic lesion size and cellular content were analyzed using histology and immunofluorescence. Vascular protein expression and IKKα kinase activity were quantified by Luminex multiplex immuno-assay and ELISA. A vascular site-specific IKKα expression and kinase activation profile was revealed, with higher total IKKα protein levels in aortic root but increased IKKα phosphorylation, representing activated IKKα, in the aortic arch. This was associated with a vascular site-specific effect of IkkαAA/AA knock-in on atherosclerosis: in the aortic root, IkkαAA/AA knock-in decreased lesion size by 22.0 ± 7.7% (p < 0.01), reduced absolute lesional smooth muscle cell numbers and lowered pro-atherogenic MMP2. In contrast, IkkαAA/AA knock-in increased lesion size in the aortic arch by 43.7 ± 20.1% (p < 0.001), increased the abundance of lesional...Continue Reading

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Mentioned in this Paper

Immunofluorescence Assay
Size
Site-Specific DNA-Methyltransferase (Adenine-Specific)
Histology Procedure
Diet, Western
Immunodeficient Mouse
Conserved helix-loop-helix ubiquitous kinase
Myocytes, Smooth Muscle
Inhibitors
Matrix Metalloproteinase 2

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