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.

Whole Transcriptome Analysis of Hypertension Induced Cardiac Injury Using Deep Sequencing

“…They also showed the accuracy and precision of RNA-Seq in quantifying the gene expression levels [36]. In the study of Dang, the author used microarrays analyzing the gene expression profiles in the heart after Ang II infusion [37]. The microarray results identified 1,489 differentially expressed genes, while our results showed 1,801 genes were differentially expressed after Ang II infusion at 1, 3 and 7 days.…”

Cardiac Ablation of SOCS3 Aggravates DOCA-Salt-Induced Hypertrophic Remodeling by Activation of Gp130-Dependent Signaling in Mice

“…The ejection fraction (EF), fractional shortening (FS), left ventricular anterior wall thickness at diastole (LVAW;d), left ventricular posterior wall thickness at diastole (LVPW;d), left ventricular inner diameter at diastole (LVID;d), left ventricular anterior wall thickness at systole (LVAW;s), and left ventricular posterior wall thickness at systole (LVPW;s) and left ventricular inner diameter at systole (LVID;s) were measured digitally on the M-mode tracings and averaged from at least 3 separate cardiac cycles. EF(%)=100*((LV Vol;d - LV Vol;s)/LV Vol;d); LV Vol;d(ul)=7.0/(2.4+LVID;d)* LVID;d 3 ; LV Vol;s(ul)=7.0/(2.4+LVID;s)* LVID;s 3 [16]. …”

Kaempferol Alleviates Angiotensin II-Induced Cardiac Dysfunction and Interstitial Fibrosis in Mice

“…After two weeks, C57BL/6 mice were subjected to either chronic cardiac remodelling generated by AngII infusion or saline as the control group [23]. Mice were randomly assigned into the following four groups: Saline (Sal), KAE (i.p., 10 mg/kg BW, dissolved in 100 µL of PBS), AngII (1.1mg/kg/day) 2W and AngII+KAE 2W.…”

“…Total RNA was extracted using TRIZOL reagent as previously described [23], which was reversely transcribed. The first-strand cDNA was used for quantitative real-time PCR to quantify mRNA expression with GAPDH as a normalized control.…”