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http://purl.uniprot.org/citations/15312879http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15312879http://www.w3.org/2000/01/rdf-schema#comment"

Objectives

We examined the effects of early treatment with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin on the progression of glucose intolerance and cardiovascular remodeling in a model of spontaneously developing type II diabetes mellitus (DM), the Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

Background

Clinical trials showed that pravastatin prevented new-onset DM in hypercholesterolemic patients, and that it was effective in prevention of cardiovascular events in diabetics.

Methods

The OLETF rats were treated with pravastatin (100 mg/kg/day) from 5 weeks of age and compared with age-matched untreated OLETF rats and normal Long-Evans Tokushima Otsuka (LETO) rats on serial oral glucose tolerance tests (OGTT) and Doppler echocardiography and on histopathological/biochemical analyses of the heart at 30 weeks.

Results

The OGTT revealed that 40% and 89% of untreated OLETF rats were diabetic at 20 and 30 weeks, respectively, but 0% and only 30%, respectively, were diabetic in the treated OLETF. Left ventricular diastolic function was found impaired from 20 weeks in untreated OLETF but remained normal in the treated-OLETF. The wall-to-lumen ratio and perivascular fibrosis of coronary arteries were increased in untreated-OLETF but were limited in the treated-OLETF at 30 weeks. Moreover, cardiac expressions of a fibrogenic growth factor, transforming growth factor-beta1 (TGF-beta1), and a proinflammatory chemokine, monocyte chemoattractant protein-1 (MCP-1), were increased in untreated-OLETF. However, in the treated-OLETF, overexpressions of TGF-beta1 and MCP-1 were attenuated, which was associated with overexpression of endothelial nitric oxide synthase (eNOS) (2.5-fold of control LETO).

Conclusions

Early pravastatin treatment prevented cardiovascular remodeling in the spontaneous DM model by retarding the progression of glucose intolerance, overexpressing cardiac eNOS, and inhibiting overexpressions of fibrogenic/proinflammatory cytokines."xsd:string
http://purl.uniprot.org/citations/15312879http://purl.org/dc/terms/identifier"doi:10.1016/j.jacc.2004.04.050"xsd:string
http://purl.uniprot.org/citations/15312879http://purl.uniprot.org/core/author"Chen Y."xsd:string
http://purl.uniprot.org/citations/15312879http://purl.uniprot.org/core/author"Yu Y."xsd:string
http://purl.uniprot.org/citations/15312879http://purl.uniprot.org/core/author"Takeuchi H."xsd:string
http://purl.uniprot.org/citations/15312879http://purl.uniprot.org/core/author"Sato C."xsd:string
http://purl.uniprot.org/citations/15312879http://purl.uniprot.org/core/author"Kohno M."xsd:string
http://purl.uniprot.org/citations/15312879http://purl.uniprot.org/core/author"Ohmori K."xsd:string
http://purl.uniprot.org/citations/15312879http://purl.uniprot.org/core/author"Shinomiya K."xsd:string
http://purl.uniprot.org/citations/15312879http://purl.uniprot.org/core/author"Kiyomoto H."xsd:string
http://purl.uniprot.org/citations/15312879http://purl.uniprot.org/core/author"Mizushige K."xsd:string
http://purl.uniprot.org/citations/15312879http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/15312879http://purl.uniprot.org/core/name"J Am Coll Cardiol"xsd:string
http://purl.uniprot.org/citations/15312879http://purl.uniprot.org/core/pages"904-913"xsd:string
http://purl.uniprot.org/citations/15312879http://purl.uniprot.org/core/title"Effects of pravastatin on progression of glucose intolerance and cardiovascular remodeling in a type II diabetes model."xsd:string
http://purl.uniprot.org/citations/15312879http://purl.uniprot.org/core/volume"44"xsd:string
http://purl.uniprot.org/citations/15312879http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/15312879
http://purl.uniprot.org/citations/15312879http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/15312879
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http://purl.uniprot.org/uniprot/A0A8I6AUL2http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15312879
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