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Author |
Nicol, C.J.; Adachi, M.; Akiyama, T.E.; Gonzalez, F.J. |
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Title |
PPARgamma in endothelial cells influences high fat diet-induced hypertension |
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Journal Article |
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Year |
2005 |
Publication  |
American journal of hypertension : journal of the American Society of Hypertension |
Abbreviated Journal |
Am J Hypertens |
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Volume |
18 |
Issue |
4 Pt 1 |
Pages |
549-556 |
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Keywords |
Administration, Oral; Animals; Antihypertensive Agents/pharmacology; Blood Pressure/drug effects; Diabetes Mellitus, Type 2/physiopathology; Dietary Fats/*administration & dosage/pharmacology; Dose-Response Relationship, Drug; Endothelial Cells/*metabolism; Female; Heart Rate/drug effects; Hypertension/*etiology; Ligands; Male; Mice; Mice, Knockout; PPAR gamma/*metabolism; Sodium Chloride/administration & dosage/pharmacology; Thiazolidinediones/pharmacology |
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Abstract |
BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands improve human hypertension. However, the mechanism and site of this effect remains unknown, confounded by PPARgamma expression in many cell types, including endothelial cells (ECs). METHODS: To evaluate the vascular role of PPARgamma we used a conditional null mouse model. Specific disruption of PPARgamma in ECs was created by crossing Tie2-Cre+ transgenic (T2T+) and PPARgamma-floxed (fl/fl) mice to generate PPARgamma (fl/fl)T2T+ (PPARgamma E-null) mice. Conscious 8- to 12-week-old congenic PPARgamma (fl/fl)Cre- (wild type) and PPARgamma E-null mice were examined for changes in systolic blood pressure (BP) and heart rate (HR), untreated, after 2 months of salt-loading (drinking water), and after treatment for 3 months with high fat (HF) diet alone or supplemented during the last 2 weeks with rosiglitazone (3 mg/kg/d). RESULTS: Untreated PPARgamma E-nulls were phenotypically indistinguishable from wild-type littermates. However, compared to similarly treated wild types, HF-treated PPARgamma E-nulls had significantly elevated systolic BP not seen after normal diet or salt-loading. Despite sex-dependent baseline differences, salt-loaded and HF-treated PPARgamma E-nulls of either sex had significantly elevated HR versus wild types. Interestingly, rosiglitazone improved serum insulin levels, but not HF diet-induced hypertension, in PPARgamma E-null mice. CONCLUSIONS: These results suggest that PPARgamma in ECs not only is an important regulator of hypertension and HR under stressed conditions mimicking those arising in type 2 diabetics, but also mediates the antihypertensive effects of rosiglitazone. These data add evidence supporting a beneficial role for PPARgamma-specific ligands in the treatment of hypertension, and suggest therapeutic strategies targeting ECs may prove useful. |
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Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA |
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0895-7061 |
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PMID:15831367 |
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Call Number |
refbase @ user @ |
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69 |
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Author |
Nelson, G.S. |
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Title |
Onchocerciasis |
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Journal Article |
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Year |
1970 |
Publication |
Advances in Parasitology |
Abbreviated Journal |
Adv Parasitol |
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Volume |
8 |
Issue |
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Pages |
173-224 |
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Keywords |
Africa; Animals; Anthelmintics/therapeutic use; Artiodactyla; Blindness/etiology; Cattle; Circadian Rhythm; Ddt; Diethylcarbamazine/therapeutic use; Diptera/anatomy & histology/growth & development; Dwarfism/etiology; Ecology; Eye/pathology; Feeding Behavior; Female; Geography; Haplorhini; Hernia, Femoral/etiology; Horses; Humans; Insect Vectors/growth & development; Larva/growth & development; Male; Onchocerca/classification/growth & development; *Onchocerciasis/diagnosis/drug therapy/epidemiology/immunology/pathology/prevention & control/veterinary; Primates; Serologic Tests; Skin/pathology; Skin Tests; Suramin/therapeutic use |
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0065-308X |
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PMID:4997515 |
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Equine Behaviour @ team @ |
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2738 |
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Author |
Yang, S. |
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Title |
Melioidosis research in China |
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Journal Article |
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Year |
2000 |
Publication |
Acta Tropica |
Abbreviated Journal |
Acta Trop |
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77 |
Issue |
2 |
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157-165 |
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Keywords |
Animals; Anti-Bacterial Agents/pharmacology; Burkholderia pseudomallei/drug effects/immunology/*pathogenicity; China/epidemiology; Cross Reactions; Glanders/immunology/microbiology; Horses; Humans; *Melioidosis/epidemiology/immunology/microbiology/veterinary; Seroepidemiologic Studies; Virulence |
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Abstract |
Research on melioidosis and its pathogen has been ongoing in China for more than two decades. It has been demonstrated that the natural foci are located predominantly in Hainan, Guangdong and Guangxi province, where there is a good correlation between soil isolation and the serum prevalence of antibodies to Burkholderia pseudomallei. The cases of melioidosis reported up to now are concentrated in the Hainan and Zhanjiang peninsula. Investigations on serotype, virulence, ecology, antibiotic susceptibility, whole cell analysis by gas chromatography, and genetics have led to a new understanding of the pathology of the disease. Immunological cross reactions between Burkholderia mallei and B. pseudomallei and the difference between melioidosis and glanders in horses is discussed. |
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Medical Research Institute, Yan-Ling (510507), Dongguanzhuang Road 91, Guangzhou, People's Republic of China. songyangch@hotmail.com |
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0001-706X |
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PMID:11080506 |
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Equine Behaviour @ team @ |
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2649 |
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