Gene expression profile in the early stage of angiotensin II-induced cardiac remodeling: a time series microarray study in a mouse model.

Abstract

BACKGROUND/AIMS:

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: Meng-Qiu Dang, Xue-Chen Zhao, Song Lai, Xia Wang, Lei Wang, Yun-Long Zhang, Yang Liu, Xiao-Hong Yu, Ying Liu, Hui-Hua Li, Yun-Long Xia
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 35 Issue 2 Pg. 467-76 ( 2015) ISSN: 1421-9778 [Electronic] Germany
• PMID: 25613478 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• Serpin E2
• Serpine2 protein, mouse
• Angiotensin II

Topics

• Angiotensin II (metabolism)
• Animals
• Blood Pressure (drug effects)
• Disease Models, Animal
• Gene Expression Profiling
• Gene Expression Regulation (drug effects)
• Male
• Mice
• Mice, Inbred C57BL
• Myocardium (metabolism)
• Oligonucleotide Array Sequence Analysis (methods)
• Serpin E2 (genetics)
• Time Factors