Exploring regulatory mechanisms of atrial myocyte hypertrophy of mitral regurgitation through gene expression profiling analysis: Role of NFAT in cardiac hypertrophy

Tzu Hao Chang, Mien Cheng Chen, Jen Ping Chang, Hsien Da Huang, Wan Chun Ho, Yu Sheng Lin, Kuo Li Pan, Yao Kuang Huang, Wen Hao Liu, Chia Chen Wu

Research output: Contribution to journalArticle

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Abstract

Background Left atrial enlargement in mitral regurgitation (MR) predicts a poor prognosis. The regulatory mechanisms of atrial myocyte hypertrophy of MR patients remain unknown. Methods and Results This study comprised 14 patients with MR, 7 patients with aortic valve disease (AVD), and 6 purchased samples from normal subjects (NC). We used microarrays, enrichment analysis and quantitative RT-PCR to study the gene expression profiles in the left atria. Microarray results showed that 112 genes were differentially up-regulated and 132 genes were differentially down-regulated in the left atria between MR patients and NC. Enrichment analysis of differentially expressed genes demonstrated that "NFAT in cardiac hypertrophy" pathway was not only one of the significant associated canonical pathways, but also the only one predicted with a non-zero score of 1.34 (i.e. activated) through Ingenuity Pathway Analysis molecule activity predictor. Ingenuity Pathway Analysis Global Molecular Network analysis exhibited that the highest score network also showed high association with cardiac related pathways and functions. Therefore, 5 NFAT associated genes (PPP3R1, PPP3CB, CAMK1, MEF2C, PLCE1) were studies for validation. The mRNA expressions of PPP3CB and MEF2C were significantly up-regulated, and CAMK1 and PPP3R1 were significantly down-regulated in MR patients compared to NC. Moreover, MR patients had significantly increased mRNA levels of PPP3CB, MEF2C and PLCE1 compared to AVD patients. The atrial myocyte size of MR patients significantly exceeded that of the AVD patients and NC. Conclusions Differentially expressed genes in the "NFAT in cardiac hypertrophy" pathway may play a critical role in the atrial myocyte hypertrophy of MR patients.

Original languageEnglish
Article number0166791
JournalPLoS One
Volume11
Issue number12
DOIs
Publication statusPublished - Dec 1 2016

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Cardiomegaly
Mitral Valve Insufficiency
Gene Expression Profiling
hypertrophy
Gene expression
myocytes
Muscle Cells
Hypertrophy
Genes
gene expression
Microarrays
Aortic Diseases
Aortic Valve
Messenger RNA
Electric network analysis
Heart Atria
genes
Association reactions
Molecules
Validation Studies

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Exploring regulatory mechanisms of atrial myocyte hypertrophy of mitral regurgitation through gene expression profiling analysis : Role of NFAT in cardiac hypertrophy. / Chang, Tzu Hao; Chen, Mien Cheng; Chang, Jen Ping; Huang, Hsien Da; Ho, Wan Chun; Lin, Yu Sheng; Pan, Kuo Li; Huang, Yao Kuang; Liu, Wen Hao; Wu, Chia Chen.

In: PLoS One, Vol. 11, No. 12, 0166791, 01.12.2016.

Research output: Contribution to journalArticle

Chang, Tzu Hao ; Chen, Mien Cheng ; Chang, Jen Ping ; Huang, Hsien Da ; Ho, Wan Chun ; Lin, Yu Sheng ; Pan, Kuo Li ; Huang, Yao Kuang ; Liu, Wen Hao ; Wu, Chia Chen. / Exploring regulatory mechanisms of atrial myocyte hypertrophy of mitral regurgitation through gene expression profiling analysis : Role of NFAT in cardiac hypertrophy. In: PLoS One. 2016 ; Vol. 11, No. 12.
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abstract = "Background Left atrial enlargement in mitral regurgitation (MR) predicts a poor prognosis. The regulatory mechanisms of atrial myocyte hypertrophy of MR patients remain unknown. Methods and Results This study comprised 14 patients with MR, 7 patients with aortic valve disease (AVD), and 6 purchased samples from normal subjects (NC). We used microarrays, enrichment analysis and quantitative RT-PCR to study the gene expression profiles in the left atria. Microarray results showed that 112 genes were differentially up-regulated and 132 genes were differentially down-regulated in the left atria between MR patients and NC. Enrichment analysis of differentially expressed genes demonstrated that {"}NFAT in cardiac hypertrophy{"} pathway was not only one of the significant associated canonical pathways, but also the only one predicted with a non-zero score of 1.34 (i.e. activated) through Ingenuity Pathway Analysis molecule activity predictor. Ingenuity Pathway Analysis Global Molecular Network analysis exhibited that the highest score network also showed high association with cardiac related pathways and functions. Therefore, 5 NFAT associated genes (PPP3R1, PPP3CB, CAMK1, MEF2C, PLCE1) were studies for validation. The mRNA expressions of PPP3CB and MEF2C were significantly up-regulated, and CAMK1 and PPP3R1 were significantly down-regulated in MR patients compared to NC. Moreover, MR patients had significantly increased mRNA levels of PPP3CB, MEF2C and PLCE1 compared to AVD patients. The atrial myocyte size of MR patients significantly exceeded that of the AVD patients and NC. Conclusions Differentially expressed genes in the {"}NFAT in cardiac hypertrophy{"} pathway may play a critical role in the atrial myocyte hypertrophy of MR patients.",
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T1 - Exploring regulatory mechanisms of atrial myocyte hypertrophy of mitral regurgitation through gene expression profiling analysis

T2 - Role of NFAT in cardiac hypertrophy

AU - Chang, Tzu Hao

AU - Chen, Mien Cheng

AU - Chang, Jen Ping

AU - Huang, Hsien Da

AU - Ho, Wan Chun

AU - Lin, Yu Sheng

AU - Pan, Kuo Li

AU - Huang, Yao Kuang

AU - Liu, Wen Hao

AU - Wu, Chia Chen

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Y1 - 2016/12/1

N2 - Background Left atrial enlargement in mitral regurgitation (MR) predicts a poor prognosis. The regulatory mechanisms of atrial myocyte hypertrophy of MR patients remain unknown. Methods and Results This study comprised 14 patients with MR, 7 patients with aortic valve disease (AVD), and 6 purchased samples from normal subjects (NC). We used microarrays, enrichment analysis and quantitative RT-PCR to study the gene expression profiles in the left atria. Microarray results showed that 112 genes were differentially up-regulated and 132 genes were differentially down-regulated in the left atria between MR patients and NC. Enrichment analysis of differentially expressed genes demonstrated that "NFAT in cardiac hypertrophy" pathway was not only one of the significant associated canonical pathways, but also the only one predicted with a non-zero score of 1.34 (i.e. activated) through Ingenuity Pathway Analysis molecule activity predictor. Ingenuity Pathway Analysis Global Molecular Network analysis exhibited that the highest score network also showed high association with cardiac related pathways and functions. Therefore, 5 NFAT associated genes (PPP3R1, PPP3CB, CAMK1, MEF2C, PLCE1) were studies for validation. The mRNA expressions of PPP3CB and MEF2C were significantly up-regulated, and CAMK1 and PPP3R1 were significantly down-regulated in MR patients compared to NC. Moreover, MR patients had significantly increased mRNA levels of PPP3CB, MEF2C and PLCE1 compared to AVD patients. The atrial myocyte size of MR patients significantly exceeded that of the AVD patients and NC. Conclusions Differentially expressed genes in the "NFAT in cardiac hypertrophy" pathway may play a critical role in the atrial myocyte hypertrophy of MR patients.

AB - Background Left atrial enlargement in mitral regurgitation (MR) predicts a poor prognosis. The regulatory mechanisms of atrial myocyte hypertrophy of MR patients remain unknown. Methods and Results This study comprised 14 patients with MR, 7 patients with aortic valve disease (AVD), and 6 purchased samples from normal subjects (NC). We used microarrays, enrichment analysis and quantitative RT-PCR to study the gene expression profiles in the left atria. Microarray results showed that 112 genes were differentially up-regulated and 132 genes were differentially down-regulated in the left atria between MR patients and NC. Enrichment analysis of differentially expressed genes demonstrated that "NFAT in cardiac hypertrophy" pathway was not only one of the significant associated canonical pathways, but also the only one predicted with a non-zero score of 1.34 (i.e. activated) through Ingenuity Pathway Analysis molecule activity predictor. Ingenuity Pathway Analysis Global Molecular Network analysis exhibited that the highest score network also showed high association with cardiac related pathways and functions. Therefore, 5 NFAT associated genes (PPP3R1, PPP3CB, CAMK1, MEF2C, PLCE1) were studies for validation. The mRNA expressions of PPP3CB and MEF2C were significantly up-regulated, and CAMK1 and PPP3R1 were significantly down-regulated in MR patients compared to NC. Moreover, MR patients had significantly increased mRNA levels of PPP3CB, MEF2C and PLCE1 compared to AVD patients. The atrial myocyte size of MR patients significantly exceeded that of the AVD patients and NC. Conclusions Differentially expressed genes in the "NFAT in cardiac hypertrophy" pathway may play a critical role in the atrial myocyte hypertrophy of MR patients.

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