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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
  • 1Department 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
  • 2Bioland Laboratory, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510005, China
  • 3Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
Received: July 8, 2020Accepted: March 2, 2021Published: April 23, 2021
https://doi.org/10.18632/aging.202879

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.

Abstract

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.