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

研究成果: 雜誌貢獻文章同行評審

9 引文 斯高帕斯(Scopus)

摘要

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 <0.5 (Log2FC < -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.

原文英語
頁(從 - 到)599-620
頁數22
期刊Translational Research
165
發行號5
DOIs
出版狀態已發佈 - 5月 1 2015

ASJC Scopus subject areas

  • 公共衛生、環境和職業健康
  • 生物化學(醫學)
  • 生理學(醫學)

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