Soluble epoxide hydrolase is a susceptibility factor for heart failure in a rat model of human disease
| العنوان: | Soluble epoxide hydrolase is a susceptibility factor for heart failure in a rat model of human disease |
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| المؤلفون: | Herbert Schulz, Bruce D. Hammock, Martin Vingron, Friedrich C. Luft, Volkmar Gross, Giannino Patone, Wolf-Hagen Schunck, Klaus Lindpaintner, Robert Fischer, Cosima Schmidt, Matthias Heinig, Oliver Hummel, Steven M. Weldon, Claudia Gosele, Judith Fischer, Svetlana Paskas, Henrike Maatz, Kathrin Saar, Norbert Hubner, Arnd Heuser, Stuart A. Cook, Jan Monti, Klaus Rohde, Rainer Dietz, Alexander Schirdewan |
| المصدر: | Nat Genet |
| بيانات النشر: | Springer Science and Business Media LLC, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Epoxide hydrolase 2, medicine.medical_specialty, Heart disease, Genetic Linkage, Quantitative Trait Loci, Biology, Polymorphism, Single Nucleotide, Rats, Mutant Strains, Article, Mice, Genetic linkage, Internal medicine, Genetics, medicine, Animals, Humans, Genetic Predisposition to Disease, Promoter Regions, Genetic, Epoxide hydrolase, Sequence Deletion, Epoxide Hydrolases, Heart Failure, Mice, Knockout, chemistry.chemical_classification, Polymorphism, Genetic, Gene Expression Profiling, Myocardium, Chromosome Mapping, Sequence Analysis, DNA, medicine.disease, Rats, Transcription Factor AP-1, Gene expression profiling, Disease Models, Animal, Endocrinology, Enzyme, chemistry, Heart failure, Hypertension, Knockout mouse |
| الوصف: | We aimed to identify genetic variants associated with heart failure by using a rat model of the human disease. We performed invasive cardiac hemodynamic measurements in F(2) crosses between spontaneously hypertensive heart failure (SHHF) rats and reference strains. We combined linkage analyses with genome-wide expression profiling and identified Ephx2 as a heart failure susceptibility gene in SHHF rats. Specifically, we found that cis variation at Ephx2 segregated with heart failure and with increased transcript expression, protein expression and enzyme activity, leading to a more rapid hydrolysis of cardioprotective epoxyeicosatrienoic acids. To confirm our results, we tested the role of Ephx2 in heart failure using knockout mice. Ephx2 gene ablation protected from pressure overload–induced heart failure and cardiac arrhythmias. We further demonstrated differential regulation of EPHX2 in human heart failure, suggesting a cross-species role for Ephx2 in this complex disease. |
| تدمد: | 1546-1718 1061-4036 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1ed3eba14f90743b8c26b6bee6f9bf20 https://doi.org/10.1038/ng.129 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1ed3eba14f90743b8c26b6bee6f9bf20 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15461718 10614036 |
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