Abstract
356 - Circulating EGF-Like Ligands in Obesity Increase Neointimal Formation through Upregulation of NADPH Oxidase 1
Free radical biology & medicine, Vol.100(Supplement), pp.S151-S151
11/2016
DOI: 10.1016/j.freeradbiomed.2016.10.397
Abstract
Obesity is an independent risk factor for cardiovascular disease, including atherosclerosis and restenosis. Obesity has been associated with low levels of chronic inflammation. We hypothesized that in chronic inflammatory disease states, like obesity, circulating epidermal growth factor (EGF)-like ligands accelerate vascular disease by upregulating the Nox1 NADPH oxidase expression and activity. Ten week old male and female mice were fed a 16% fat (Teklad, TD.94059, n=7) or normal chow (lean, n=9) diet for 15 weeks (weight 41.6 vs. 27.9 gms). Heparin bound (HB)-EGF levels were increased 2.9-fold in serum from obese mice as compared to lean litter mates. Thirty days after carotid ligation, neointimal formation was greater in the obese mice (intima/media area ratio 0.65 vs 0.25, obese vs. lean, p<0.05) and the systemic administration of AG1478, an EGFR inhibitor, by osmotic minipump, reduced neointimal formation in the obese mice (I/M 0.16, n=8). Lean mice exposed to increased circulationg HB-EGF by an osmotic minipump developed increased vascular expression of Nox1 (1.7-fold), but not Nox4. In cultured smooth muscle cells (SMC), HB-EGF increased Nox1 expression, NFkB activation, and cell proliferation (2.6-fold). The HB-EGF-mediated increase in cell growth was prevented by knockdown of Nox1 and by the mitochondrial targeted antioxidant, mitoTEMPO. Overexpression of Nox1 “rescued” the inhibitory effects of mitoTEMPO on SMC proliferation. These data suggest that obesity is associated with increased circulating EGF-ligands which contribute to the development of cardiovascular disease by a mechanism that involves mitochondrial ROS-induced ROS and the increased expression of Nox1.
Details
- Title: Subtitle
- 356 - Circulating EGF-Like Ligands in Obesity Increase Neointimal Formation through Upregulation of NADPH Oxidase 1
- Creators
- Brandon M Schickling - University of IowaMaysam Takapoo - University of IowaRohan Khera - University of IowaFrancis J Miller - Duke University
- Resource Type
- Abstract
- Publication Details
- Free radical biology & medicine, Vol.100(Supplement), pp.S151-S151
- DOI
- 10.1016/j.freeradbiomed.2016.10.397
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 11/2016
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984966715902771
Metrics
1 Record Views