Abstract 16043: The Role of eNOS Signaling in Wound Healing in a Murine Model of Diet-Induced Obesity

• Published in: Circulation (New York, N.Y.) N.Y.), 2014-11, Vol.130 (suppl_2)
• Main Authors: Haberzettl, Petra, McCracken, James, Hill, Bradford G, Bhatnagar, Aruni, Conklin, Daniel J
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.130.suppl_2.16043

Abstract only Background and Rationale: Type 2-diabetes is associated with the depletion of circulating endothelial progenitor cells (EPCs) and deficits in wound healing; conditions that have been linked to decreased activity of endothelial nitric oxide synthase (eNOS). However, it is not clear how, in the context of insulin resistance, increasing eNOS would affect EPC levels and wound healing. Therefore, we measured EPC levels and recovery from hind-limb ischemia (HLI) in wild-type and eNOS-transgenic (Tg) mice in a model of diet-induced obesity. Methods and Results: Wild-type (WT) C57BL/6 and eNOS-Tg mice were placed on a low (LFD) or high fat diet (HFD). After 12 weeks, the mice were subjected to HLI, and tissue perfusion was assessed by Laser Doppler Imaging. Levels of EPCs (Flk-1+/Sca-1+-cells) were measured by flow cytometry. HFD feeding, for 4-12 weeks, decreased circulating EPC levels while the levels of EPCs in the bone marrow were increased. Insulin (100 nM; 15 min) stimulated Akt and eNOS phosphorylation in aorta of LFD, but not HFD-fed mice, indicating insulin resistance. HFD decreased plasma NOx levels and activated the pro-inflammatory NF-κBα pathway in aorta, heart, liver, skeletal muscle and adipose tissue as analyzed by Western blot analysis. Recovery of blood perfusion, 2 weeks after HLI, was significantly higher in LFD than HFD-fed mice (76±3% vs. 21±4%; p