title: Gene expression profile in the early stage of angiotensin II-induced cardiac remodeling: a time series microarray study in a mouse model.
abstract: OBJECTIVE
  Angiotensin II (Ang II) plays a critical role in the cardiac remodeling contributing to heart failure. However, the gene expression profiles induced by Ang II in the early stage of cardiac remodeling remain unknown.
  
  
  METHODS
  Wild-type male mice (C57BL/6 background, 10-weeek-old) were infused with Ang II (1500 ng/kg/min) for 7 days. Blood pressure was measured. Cardiac function and remodeling were examined by echocardiography, H&E and Masson staining. The time series microarrays were then conducted to detected gene expression profiles.
  
  
  RESULTS
  Microarray results identified that 1,489 genes were differentially expressed in the hearts at day 1, 3 and 7 of Ang II injection. These genes were further classified into 26 profiles by hierarchical cluster analysis. Of them, 4 profiles were significant (No. 19, 8, 21 and 22) and contained 904 genes. Gene Ontology showed that these genes mainly participate in metabolic process, oxidation-reduction process, extracellular matrix organization, apoptotic process, immune response, and others. Significant pathways included focal adhesion, ECM-receptor interaction, cytokine-cytokine receptor interaction, MAPK and insulin signaling pathways, which were known to play important roles in Ang II-induced cardiac remodeling. Moreover, gene co-expression networks analysis suggested that serine/cysteine peptidase inhibitor, member 1 (Serpine1, also known as PAI-1) localized in the core of the network.
  
  
  CONCLUSIONS
  Our results indicate that many genes are mainly involved in metabolism, inflammation, cardiac fibrosis and hypertrophy. Serpine1 may play a central role in the development of Ang II-induced cardiac remodeling at the early stage.
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian, PR China.
authors.forename: Meng-Qiu
authors.initials: MQ
authors.lastname: Dang
authors.forename: Xue-Chen
authors.initials: XC
authors.lastname: Zhao
authors.forename: Song
authors.initials: S
authors.lastname: Lai
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Yun-Long
authors.initials: YL
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Yu
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Li
authors.forename: Yun-Long
authors.initials: YL
authors.lastname: Xia
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D058258:Serpin E2 / Q000235:genetics*; D013997:Time Factors
chemical_list: D058258:Serpin E2; C511869:Serpine2 protein, mouse; D000804:Angiotensin II