Abstract 16417: Serum and Glucocorticoid Inducible Kinase-1 Drives Aortic Macrophage Accumulation in Hypertension and Abdominal Aortic Aneurysms

• Published in: Circulation (New York, N.Y.) N.Y.), 2018-11, Vol.138 (Suppl_1 Suppl 1), p.A16417-A16417
• Main Authors: Ruddy, Jean Marie, Grespin, Randal T, Mukherjee, Rupak, Jones, Jeffrey A
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539

IntroductionHypertensive aortic remodeling is driven by macrophage infiltration to secrete cytokines and proteases, and a subset of these patients will also develop an abdominal aortic aneurysm (AAA). The serum and glucocorticoid inducible kinase-1 (SGK-1) is a mechanosensitive kinase implicated in bypass graft remodeling.HypothesisIt is hypothesized that SGK-1 is upregulated under conditions of elevated tension to promote macrophage accumulation and contribute to AAA development.MethodsAortic vascular smooth muscle cells (VSMCs) were subjected to 12% biaxial cyclic stretch for 3 hours with subsequent harvest of mRNA and quantification of interleukin-6 (IL-6) expression by QPCR (n=4). SGK-1 activity was blocked by the selective inhibitor EMD638683 (10μM). Hypertension (HTN) was induced in C57Bl/6 mice with AngiotensinII (AngII) infusion via mini-osmotic pump (1.46mg/kg/day x21days, n=4) and terminal procedure included blood pressure quantification by tail cuff plethysmography. Abundance of SGK-1, phosphorylated SGK-1 (pSGK-1), and the mature macrophage marker F4/80, was determined by immunoblotting. AAA was induced in C57Bl/6 mice by peri-adventitial application of CaCl2 with terminal procedure at 21 days for aortic diameter assessment and immunoblot quantification of target proteins (n=4).ResultsFollowing VSMC cyclic stretch, IL-6 expression increased 1.8+/-0.3 fold compared to static conditions (p40% elevation in systolic BP (p60% (p