Unraveling regulatory mechanisms of atrial remodeling of mitral regurgitation pigs by gene expression profiling analysis

Role of type i angiotensin II receptor antagonist

Mien Cheng Chen, Jen Ping Chang, Tzu Hao Chang, Sheng Da Hsu, Hsien Da Huang, Wan Chun Ho, Feng Sheng Wang, Chang Chun Hsiao, Wen Hao Liu

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Left atrial enlargement associated with mitral regurgitation (MR) predicts a poor prognosis. However, the underlying regulatory mechanisms of atrial remodeling remain unclear. We used high-density oligonucleotide microarrays and enrichment analysis to identify the alteration of RNA expression pattern and biological processes involved in the atrial remodeling of pigs with and without MR. Gene arrays from left atria tissues were compared in 13 pigs (iatrogenic MR pigs [n = 6], iatrogenic MR pigs treated with valsartan [n = 4], and pigs without MR [n = 3]). A total of 22 genes were differentially upregulated by altered fold change >2.0 (Log2FC > 1), and 49 genes were differentially downregulated by altered fold change 2FC <-1) in the left atria of the MR pigs compared with the pigs without MR. Enrichment analysis showed that renin-angiotensin system was identified in the Kyoto Encyclopedia of Genes and Genomes pathway. Notably, 12 of the 22 upregulated genes were identified to be downregulated by valsartan and 10 of the 49 downregulated genes were identified to be upregulated by valsartan. The tissue concentrations of angiotensin II and gene expression of hypertrophic gene, myosin regulatory light chain 2, ventricular isoforms, and fibrosis-related genes were significantly increased in the MR pigs compared with pigs without MR. In conclusion, differentially expressed transcriptome and related biological pathways have been identified in the left atria of the MR pigs compared with pigs without MR. Additionally, some of the differentially expressed genes could be regulated by type I angiotensin II receptor blocker.

Original languageEnglish
Pages (from-to)599-620
Number of pages22
JournalTranslational Research
Volume165
Issue number5
DOIs
Publication statusPublished - May 1 2015

Fingerprint

Atrial Remodeling
Angiotensin Receptor Antagonists
Mitral Valve Insufficiency
Gene Expression Profiling
Gene expression
Swine
Genes
Valsartan
Heart Atria
Down-Regulation
Tissue
Encyclopedias
Myosin Light Chains
Biological Phenomena
Angiotensins
Microarrays
Renin
Oligonucleotides
Angiotensin II
Microarray Analysis

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, medical
  • Public Health, Environmental and Occupational Health

Cite this

Unraveling regulatory mechanisms of atrial remodeling of mitral regurgitation pigs by gene expression profiling analysis : Role of type i angiotensin II receptor antagonist. / Chen, Mien Cheng; Chang, Jen Ping; Chang, Tzu Hao; Hsu, Sheng Da; Huang, Hsien Da; Ho, Wan Chun; Wang, Feng Sheng; Hsiao, Chang Chun; Liu, Wen Hao.

In: Translational Research, Vol. 165, No. 5, 01.05.2015, p. 599-620.

Research output: Contribution to journalArticle

Chen, Mien Cheng ; Chang, Jen Ping ; Chang, Tzu Hao ; Hsu, Sheng Da ; Huang, Hsien Da ; Ho, Wan Chun ; Wang, Feng Sheng ; Hsiao, Chang Chun ; Liu, Wen Hao. / Unraveling regulatory mechanisms of atrial remodeling of mitral regurgitation pigs by gene expression profiling analysis : Role of type i angiotensin II receptor antagonist. In: Translational Research. 2015 ; Vol. 165, No. 5. pp. 599-620.
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