AUTHOR=Zhou Zuoqiong , Zheng Lan , Tang Changfa , Chen Zhanglin , Zhu Runkang , Peng Xiyang , Wu Xiushan , Zhu Ping 

TITLE=Identification of Potentially Relevant Genes for Excessive Exercise-Induced Pathological Cardiac Hypertrophy in Zebrafish

JOURNAL=Frontiers in Physiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2020.565307

DOI=10.3389/fphys.2020.565307

ISSN=1664-042X

ABSTRACT=<p>Exercise-induced cardiac remodeling has aroused public concern for some time, as sudden cardiac death is known to occur in athletes; however, little is known about the underlying mechanism of exercise-induced cardiac injury. In the present study, we established an excessive exercise-induced pathologic cardiac hypertrophy model in zebrafish with increased myocardial fibrosis, myofibril disassembly, mitochondrial degradation, upregulated expression of the pathological hypertrophy marker genes in the heart, contractile impairment, and cardiopulmonary function impairment. High-throughput RNA-seq analysis revealed that the differentially expressed genes were enriched in the regulation of autophagy, protein folding, and degradation, myofibril development, angiogenesis, metabolic reprogramming, and insulin and FoxO signaling pathways. FOXO proteins may be the core mediator of the regulatory network needed to promote the pathological response. Further, PPI network analysis showed that <italic>pik3c3</italic>, <italic>gapdh</italic>, <italic>fbox32</italic>, <italic>fzr1</italic>, <italic>ubox5</italic>, <italic>lmo7a</italic>, <italic>kctd7</italic>, <italic>fbxo9</italic>, <italic>lonrf1l</italic>, <italic>fbxl4</italic>, <italic>nhpb2l1b</italic>, <italic>nhp2</italic>, <italic>fbl</italic>, <italic>hsp90aa1.1</italic>, <italic>snrpd3l</italic>, <italic>dhx15</italic>, <italic>mrto4</italic>, <italic>ruvbl1</italic>, <italic>hspa8b</italic>, and <italic>faub</italic> are the hub genes that correlate with the pathogenesis of pathological cardiac hypertrophy. The underlying regulatory pathways and cardiac pressure-responsive molecules identified in the present study will provide valuable insights for the supervision and clinical treatment of pathological cardiac hypertrophy induced by excessive exercise.</p>