Aspirin prevents resistin-induced endothelial dysfunction by modulating AMPK, ROS, and Akt/eNOS signaling

Department of Physical Therapy and Graduate, Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan, Republic of China.
Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter (Impact Factor: 3.02). 01/2012; 55(4):1104-15. DOI: 10.1016/j.jvs.2011.10.011
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Fig 1. Effects of aspirin on resistin-induced reactive oxygen species (ROS) generation in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were pretreated for 2 hours with various concentrations of aspirin (10-500 μg/mL), followed by treatment with 100 ng/mL resistin for 48 hours. At the end of treatment, HUVECs were incubated with the superoxide-sensitive fluorescent probe dihydroethidium (DHE; 10 μM) for 1 hour. A, Fluorescence images show the ROS level in control cells (left) and in HUVECs stimulated with resistin (middle) in the presence of 500 μg/mL aspirin (right). B, Fluorescence intensity of HUVECs was measured with a fluorescence microplate reader. Fluorescence distribution of DHE oxidation was expressed as a percentage of increased intensity. The activities of superoxide dismutase (SOD) (C) and catalase (D) in HUVECs stimulated with resistin in the absence or presence of indicated concentrations of aspirin were determined. Data are expressed as the mean ± SEM of three independent analyses. #P < .05 vs untreated control; *P < .05 compared with resistin treatment.

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Available from: Wen-Jane Lee, Nov 18, 2014
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    • "In hyperglycemia, AMPK reduces NADPH oxidase activation and ROS generation [23], and activation of AMPK can increase the antioxidant MnSOD, which inhibits high glucose-induced intracellular and mitochondrial ROS production [24]. Additionally, AMPK suppresses the resistin-induced membrane assembly of NADPH oxidase and increases eNOS activity in endothelial cells [25]. We found that PA-induced the translocations of p47 phox and Rac-1, and AMPK suppression was abolished in the cells that were pretreated with EPA, which indicates that EPA attenuated oxidative stress and downregulation of AMPK. "
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    • "In this study we found that liraglutide activated AMPK and its substrate eNOS (Figure 4A, 4C). Activation of eNOS by AMPK increased nitric oxide (NO) synthesis [49], which scavenges superoxides [50], induces vasodilation [51] and inhibits leukocyte adhesion [52]. Thus, the observed activation of AMPK by liraglutide (Figure 4A) suggests a potential mechanism for the anti-inflammatory effects previously discussed. "
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