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      Angiogenesis in the New Zealand obese mouse model fed with high fat diet

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          Abstract

          Background

          Obesity and its complications lead to vascular injury, atherosclerosis, diabetes and pathological angiogenesis. One of the models to study the obesity and its entanglements is the New Zealand Obese mice model. Aim of this study was to check the effect of high fat diet on changes in biochemical parameters as well as on process of angiogenesis in NZO mice.

          Methods

          NZO mice were fed with standard (ST) or high fat (HF) diet for seven weeks. Body weight and serum biochemical parameters were monitored. The PECAM1 positive vessel-like structures immunostaining, as well as the gene expression of the matrigel penetrating cells by microarray (confirmed by real-time PCR method) were analyzed.

          Results

          Mice fed with HF diet developed obesity. Number of newly created vessels with lumen was correlated with hyperglycemia and animal weight gain. The number of PECAM1 positive cells in matrigel tended to increase during HF diet. Microarray results revealed changes in gene expression (activation of the oxidative stress and insulin resistance, inhibition of apoptosis and cell differentiation), however without markers of endothelial cell network maturation.

          Conclusion

          Observed changes in the NZO mice on HF diet argue for the hyperglycemia related activation of angiogenesis, leading to the formation of pathological, immature network.

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          Most cited references36

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          The signaling mechanism of ROS in tumor progression.

          Reactive oxygen species (ROS) are recently proposed to be involved in tumor metastasis which is a complicated processes including epithelial-mesenchymal transition (EMT), migration, invasion of the tumor cells and angiogenesis around the tumor lesion. ROS generation may be induced intracellularly, in either NADPH oxidase- or mitochondria-dependent manner, by growth factors and cytokines (such as TGFbeta and HGF) and tumor promoters (such as TPA) capable of triggering cell adhesion, EMT and migration. As a signaling messenger, ROS are able to oxidize the critical target molecules such as PKC and protein tyrosine phosphates (PTPs), which are relevant to tumor cell invasion. PKC contain multiple cysteine residues that can be oxidized and activated by ROS. Inactivation of multiple PTPs by ROS may relieve the tyrosine phosphorylation-dependent signaling. Two of the down-stream molecules regulated by ROS are MAPK and PAK. MAPKs cascades were established to be a major signal pathway for driving tumor cell metastasis, which are mediated by PKC, TGF-beta/Smad and integrin-mediated signaling. PAK is an effector of Rac-mediated cytoskeletal remodeling that is responsible for cell migration and angiogenesis. There are several transcriptional factors such as AP1, Ets, Smad and Snail regulating a lot of genes relevant to metastasis. AP-1 and Smad can be activated by PKC activator and TGF-beta1, respectively, in a ROS dependent manner. On the other hand, Est-1 can be upregulated by H2O2 via an antioxidant response element in the promoter. The ROS-regulated genes relevant to EMT and metastasis include E-cahedrin, integrin and MMP. Comprehensive understanding of the ROS-triggered signaling transduction, transcriptional activation and regulation of gene expressions will help strengthen the critical role of ROS in tumor progression and devising strategy for chemo-therapeutic interventions.
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            Hypertension and associated metabolic abnormalities--the role of insulin resistance and the sympathoadrenal system.

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              Biological action of leptin as an angiogenic factor.

              Leptin is a hormone that regulates food intake, and its receptor (OB-Rb) is expressed primarily in the hypothalamus. Here, it is shown that OB-Rb is also expressed in human vasculature and in primary cultures of human endothelial cells. In vitro and in vivo assays revealed that leptin has angiogenic activity. In vivo, leptin induced neovascularization in corneas from normal rats but not in corneas from fa/fa Zucker rats, which lack functional leptin receptors. These observations indicate that the vascular endothelium is a target for leptin and suggest a physiological mechanism whereby leptin-induced angiogenesis may facilitate increased energy expenditure.
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                Author and article information

                Journal
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central
                1476-511X
                2009
                6 April 2009
                : 8
                : 13
                Affiliations
                [1 ]Department of Clinical Biochemistry, Collegium Medicum, Jagiellonian University, Cracow, Poland
                [2 ]Postgraduate School of Molecular Medicine, 61 Żwirki i Wigury Str., 02-091 Warsaw, Poland
                [3 ]Department of Pathomorphology, Collegium Medicum, Jagiellonian University, Cracow, Poland
                [4 ]German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany
                Article
                1476-511X-8-13
                10.1186/1476-511X-8-13
                2674043
                19344534
                917a305a-56ba-4d79-9a4c-f3dcdf66a7af
                Copyright © 2009 Balwierz et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 January 2009
                : 6 April 2009
                Categories
                Research

                Biochemistry
                Biochemistry

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