Research Paper Volume 13, Issue 10 pp 13585—13614

Characterizing a long-term chronic heart failure model by transcriptomic alterations and monitoring of cardiac remodeling

Yingqi Zhu1, , Qiancheng Wang1, , Hairuo Lin1, , Kaitong Chen1, , Cankun Zheng1, , Lin Chen1, , Siyuan Ma1, , Wangjun Liao3, , Jianping Bin1, , Yulin Liao1,2, ,

  • 1 Department of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Lab of Shock and Microcirculation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
  • 2 Bioland Laboratory, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510005, China
  • 3 Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

Received: July 8, 2020       Accepted: March 2, 2021       Published: April 23, 2021
How to Cite

Copyright: © 2021 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The long-term characteristics of transcriptomic alterations and cardiac remodeling in chronic heart failure (CHF) induced by myocardial infarction (MI) in mice are not well elucidated. This study aimed to reveal the dynamic changes in the transcriptome and cardiac remodeling in post-MI mice over a long time period. Monitoring C57BL/6 mice with MI for 8 months showed that approximately 44% of mice died of cardiac rupture in the first 2 weeks and others survived to 8 months with left ventricular (LV) aneurysm. The transcriptomic profiling analysis of cardiac tissues showed that the Integrin and WNT pathways were activated at 8 months after MI while the metabolism-related pathways were inversely inhibited. Subsequent differential analysis at 1 and 8 months post-MI revealed significant enrichments in biological processes, including consistent regulation of metabolism-related pathways. Moreover, echocardiographic monitoring showed a progressive increase in LV dimensions and a decrease in the LV fractional shortening during the first 4 weeks, and these parameters progressed at a lower rate till 8 months. A similar trend was found in the invasive LV hemodynamics, cardiac morphological and histological analyses. These results suggested that mouse MI model is ideal for long-term studies, and transcriptomic findings may provide new CHF therapeutic targets.


CHF: chronic heart failure; MI: myocardial infarction; LV: left ventricular; RNA-seq: RNA sequencing; PCA: Principal Component Analysis; GO: Gene Ontology; WGCNA: Weighted Gene Co-expression Network Analysis; GSEA: Gene Set Enrichment Analysis; ECG: electrocardiogram; LCA: left coronary artery; TTC: Triphenyl tetrazolium chloride; LVESd: Left ventricular end-systolic diameters; LVEDd: Left ventricular end-diastolic diameters; LVFS: Left ventricular fractional shortening; LVEF: Left ventricular ejection fraction; LVSP: Left ventricular systolic pressure; LVEDP: Left ventricular end diastolic pressure; dp/dt max/min: maximum/minimum rates of change in the LV pressure; τ: the exponential time constant of relaxation; HE: hematoxylin-eosin; Myh6: alpha-myosin heavy chain gene; Myh7: beta-myosin heavy chain gene; ANP: atrial natriuretic peptide gene; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; MAD: absolute deviation of the median; SEM: standard error of mean; LDHA/B: lactate dehydrogenase A/B; MDH2: malate dehydrogenase 2; PDK4/2: pyruvate dehydrogenase kinase 4/2; PDP1: pyruvate dehydrogenase phosphatase catalytic subunit 1; PDHA1/2: pyruvate dehydrogenase E1 alpha 1/2 subunits; EGO: Enrich Gene Ontology; GGO: Group Gene Ontology.