Microarray analysis of gene expression during early stages of mild and severe cardiac hypertrophy.
Familial hypertrophic cardiomyopathy (FHC) is a disease characterized by ventricular hypertrophy, fibrosis, and aberrant systolic and/or diastolic function. We previously developed two transgenic mouse models that carry FHC-associated mutations in alpha-tropomyosin (TM): FHC alpha-TM175 mice show patchy areas of mild ventricular disorganization and limited hypertrophy, whereas FHC alpha-TM180 mice exhibit severe hypertrophy and fibrosis and die within 6 mo. To obtain a better understanding of the molecular mechanisms associated with the early onset of cardiac hypertrophy, we conducted a detailed comparative analysis of gene expression in 2.5-mo-old control, FHC alpha-TM175, and alpha-TM180 ventricular tissue. Results show that 754 genes (from a total of 22,600) were differentially expressed between the nontransgenic (NTG) and the FHC hearts. There are 178 differentially regulated genes between NTG and the FHC alpha-TM175 hearts, 388 genes are differentially expressed between NTG and FHC alpha-TM180 hearts, and 266 genes are differentially expressed between FHC alpha-TM175 and FHC alpha-TM180 hearts. Genes that exhibit the largest increase in expression belong to the "secreted/extracellular matrix" category, and those with the most significant decrease in expression are associated with "metabolic enzymes." Confirmation of the microarray analysis was conducted by quantitative real-time PCR on gene transcripts commonly associated with cardiac hypertrophy.
Rajan
Sudarsan
S
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Williams
Sarah S
SS
Jagatheesan
Ganapathy
G
Ahmed
Rafeeq P H
RP
Fuller-Bicer
Geraldine
G
Schwartz
Arnold
A
Aronow
Bruce J
BJ
Wieczorek
David F
DF
D000818:Animals; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006321:Heart / Q000503:physiopathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D013045:Species Specificity; D014335:Tropomyosin / Q000235:genetics*
D014335:Tropomyosin