Dataset Information

Gene remodeling in type 2 diabetic cardiomyopathy and its phenotypic rescue with SERCA2a.

ABSTRACT:

Background/aim

Diabetes-associated myocardial dysfunction results in altered gene expression in the heart. We aimed to investigate the changes in gene expression profiles accompanying diabetes-induced cardiomyopathy and its phenotypic rescue by restoration of SERCA2a expression.

Methods/results

Using the Otsuka Long-Evans Tokushima Fatty rat model of type 2 diabetes and the Agilent rat microarray chip, we analyzed gene expression by comparing differential transcriptional changes in age-matched control versus diabetic hearts and diabetic hearts that received gene transfer of SERCA2a. Microarray expression profiles of selected genes were verified with real-time qPCR and immunoblotting. Our analysis indicates that diabetic cardiomyopathy is associated with a downregulation of transcripts. Diabetic cardiomyopathic hearts have reduced levels of SERCA2a. SERCA2a gene transfer in these hearts reduced diabetes-associated hypertrophy, and differentially modulated the expression of 76 genes and reversed the transcriptional profile induced by diabetes. In isolated cardiomyocytes in vitro, SERCA2a overexpression significantly modified the expression of a number of transcripts known to be involved in insulin signaling, glucose metabolism and cardiac remodeling.

Conclusion

This investigation provided insight into the pathophysiology of cardiac remodeling and the potential role of SERCA2a normalization in multiple pathways in diabetic cardiomyopathy.

SUBMITTER: Karakikes I

PROVIDER: S-EPMC2714457 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Publications

Gene remodeling in type 2 diabetic cardiomyopathy and its phenotypic rescue with SERCA2a.

Karakikes Ioannis I Kim Maengjo M Hadri Lahouaria L Sakata Susumu S Sun Yezhou Y Zhang Weijia W Chemaly Elie R ER Hajjar Roger J RJ Lebeche Djamel D

PloS one 20090731 7

<h4>Background/aim</h4>Diabetes-associated myocardial dysfunction results in altered gene expression in the heart. We aimed to investigate the changes in gene expression profiles accompanying diabetes-induced cardiomyopathy and its phenotypic rescue by restoration of SERCA2a expression.<h4>Methods/results</h4>Using the Otsuka Long-Evans Tokushima Fatty rat model of type 2 diabetes and the Agilent rat microarray chip, we analyzed gene expression by comparing differential transcriptional changes i ...[more]

PMID: 19649297

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Dataset Information

Gene remodeling in type 2 diabetic cardiomyopathy and its phenotypic rescue with SERCA2a.

Background/aim

Methods/results

Conclusion

Publications

Gene remodeling in type 2 diabetic cardiomyopathy and its phenotypic rescue with SERCA2a.

Similar Datasets

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