miRNA-Mediated Suppression of a Cardioprotective Cardiokine as a Novel Mechanism Exacerbating Post-MI Remodeling by Sleep Breathing Disorders.

Authors

• Yunhui Du
• Xiao Wang
• Linyi Li
• Wenjing Hao
• Huina Zhang
• Yu Li
• Yanwen Qin
• Shaoping Nie
• Theodore A Christopher
• Bernard L Lopez
• Wayne Bond Lau
• Yajing Wang
• Xin-Liang Ma
• Yongxiang Wei

Publication/Presentation Date

1-17-2020

Abstract

RATIONALE: Obstructive sleep apnea-hypopnea syndrome, a sleep breathing disorder in which chronic intermittent hypoxia (CIH) is the primary pathology, is associated with multiple cardiovascular diseases. However, whether and how CIH may affect cardiac remodeling following myocardial infarction (MI) remains unknown.

OBJECTIVE: To determine whether CIH exposure at different periods of MI may exacerbate post-MI heart failure and to identify the mechanisms underlying CIH-exacerbated post-MI remodeling.

METHODS AND RESULTS: Adult male mice were subjected to MI (4 weeks) with and without CIH (4 or 8 weeks). CIH before MI (CIH+MI) had no significant effect on post-MI remodeling. However, double CIH exposure (CIH+MI+CIH) or CIH only during the MI period (MI+CIH) significantly exacerbated pathological remodeling and reduced survival rate. Mechanistically, CIH activated TGF-β (tumor growth factor-β)/Smad (homologs of both the Drosophila protein MAD and the C. elegans protein SMA) signaling and enhanced cardiac epithelial to mesenchymal transition, markedly increasing post-MI cardiac fibrosis. Transcriptome analysis revealed that, among 15 genes significantly downregulated (MI+CIH versus MI),

CONCLUSIONS: This study provides the first evidence that MI+CIH upregulates miR-214-3p, suppresses cardiac CTRP9 (C1q tumor necrosis factor-related protein-9) expression, and exacerbates cardiac remodeling, suggesting that CTRP9 may be a novel therapeutic target against pathological remodeling in MI patients with obstructive sleep apnea-hypopnea syndrome.

Volume

126

Issue

2

First Page

212

Last Page

228

ISSN

1524-4571

Published In/Presented At

Du, Y., Wang, X., Li, L., Hao, W., Zhang, H., Li, Y., Qin, Y., Nie, S., Christopher, T. A., Lopez, B. L., Lau, W. B., Wang, Y., Ma, X. L., & Wei, Y. (2020). miRNA-Mediated Suppression of a Cardioprotective Cardiokine as a Novel Mechanism Exacerbating Post-MI Remodeling by Sleep Breathing Disorders. Circulation research, 126(2), 212–228. https://doi.org/10.1161/CIRCRESAHA.119.315067

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

31694459

Department(s)

Administration and Leadership

Document Type

Article