Gene expression patterns and related pathways in the hearts of rhesus monkeys subjected to prolonged myocardial ischemia

Author:

Liu Xiaojuan12,Zhang Jingyao13,Li Pengfei14,Han Pengfei1,Kang Y James1,Zhang Wenjing5ORCID

Affiliation:

1. Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu 610041, China

2. Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China

3. Core Facilities of West China Hospital, Sichuan University, Chengdu 610041, China

4. Key Laboratory of Molecular Pathology, Inner Mongolia Medical University, Hohhot 010059, China

5. Department of Genetics, Genomics and Informatics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA

Abstract

After myocardial infarction (MI) occurs, progressive pathological cardiac remodeling results in heart dysfunction and even heart failure during the following months or years. The present study explored the molecular mechanisms underlying the late phase of MI at the global transcript level. A rhesus monkey model of myocardial ischemia induced by left anterior descending (LAD) artery ligation was established, and the heart tissue was collected eight weeks after ligation for transcriptome analysis by DNA microarray technology. Differentially expressed genes in the core infarcted area and remote infarcted area of the ischemic heart were detected with significance analysis of microarray (SAM), and related pathways were detected by Gene Ontology (GO)/pathway analysis. We found that compared to the sham condition, prolonged ischemia increased the levels of 941 transcripts, decreased the levels of 380 transcripts in the core infarcted area, and decreased the levels of 8 transcripts in the remote area in monkey heart tissue. Loss of coordination between the expression of genes, including natriuretic peptide A ( NPPA), NPPB, and corin (Corin, serine peptidase), may aggravate cardiac remodeling. Furthermore, imbalance in the enriched significantly changed pathways, including fibrosis-related pathways, cardioprotective pathways, and the cardiac systolic pathway, likely also plays a key role in regulating the development of heart remodeling.

Funder

National Natural Science Foundation of China

Yunnan Province Basic Research Program Youth Project

Publisher

Frontiers Media SA

Subject

General Biochemistry, Genetics and Molecular Biology

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