title: Gene remodeling in type 2 diabetic cardiomyopathy and its phenotypic rescue with SERCA2a.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  This investigation provided insight into the pathophysiology of cardiac remodeling and the potential role of SERCA2a normalization in multiple pathways in diabetic cardiomyopathy.
authors: Cardiovascular Research Center, Mount Sinai School of Medicine, New York, New York, United States of America.
authors: Ioannis
authors: I
authors: Karakikes
authors: Maengjo
authors: M
authors: Kim
authors: Lahouaria
authors: L
authors: Hadri
authors: Susumu
authors: S
authors: Sakata
authors: Yezhou
authors: Y
authors: Sun
authors: Weijia
authors: W
authors: Zhang
authors: Elie R
authors: ER
authors: Chemaly
authors: Roger J
authors: RJ
authors: Hajjar
authors: Djamel
authors: D
authors: Lebeche
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D020869:Gene Expression Profiling; D006331:Heart Diseases / Q000150:complications / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D051381:Rats; D020318:Rats, Long-Evans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases