Microarray analysis of gene expression during early stages of mild and severe cardiac hypertrophy

被引:32
作者
Rajan, Sudarsan
Williams, Sarah S.
Jagatheesan, Ganapathy
Ahmed, Rafeeq P. H.
Fuller-Bicer, Geraldine
Schwartz, Arnold
Aronow, Bruce J.
Wieczorek, David F. [1 ]
机构
[1] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA
[2] Childrens Hosp, Med Ctr, Div Biomed Informat, Cincinnati, OH 45229 USA
[3] Univ Cincinnati, Coll Med, Dept Surg, Inst Mol Pharmacol & Biophys, Cincinnati, OH 45267 USA
关键词
tropomyosin; cardiomyopathy; familial hypertrophic cardiomyopathy mutations; microarray;
D O I
10.1152/physiolgenomics.00072.2006
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:309 / 317
页数:9
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