Sex differences in cardiac transcriptomic response to neonatal sleep apnea

Emily C. Cheung, Department of Biomedical Engineering, The George Washington University, Washington, District of Columbia, USA.
Anna Nilsson, Department of Anatomy, Biochemistry & Physiology, University of Hawaii, Honolulu, Hawaii, USA.
Ian Venter, Department of Anatomy, Biochemistry & Physiology, University of Hawaii, Honolulu, Hawaii, USA.
Grant Kowalik, Department of Biomedical Engineering, The George Washington University, Washington, District of Columbia, USA.
Caitlin Ribeiro, Department of Pharmacology and Physiology, The George Washington University, Washington, District of Columbia, USA.
Jeannette Rodriguez, Department of Biomedical Engineering, The George Washington University, Washington, District of Columbia, USA.
Kiralee Kuraoka, Department of Anatomy, Biochemistry & Physiology, University of Hawaii, Honolulu, Hawaii, USA.
Rebekah Russo, Department of Biomedical Engineering, The George Washington University, Washington, District of Columbia, USA.
Joan B. Escobar, Department of Pharmacology and Physiology, The George Washington University, Washington, District of Columbia, USA.
Bridget R. Alber, Department of Biomedical Engineering, The George Washington University, Washington, District of Columbia, USA.
David Mendelowitz, Department of Pharmacology and Physiology, The George Washington University, Washington, District of Columbia, USA.
Matthew W. Kay, Department of Biomedical Engineering, The George Washington University, Washington, District of Columbia, USA.
Kathryn J. Schunke, Department of Biomedical Engineering, The George Washington University, Washington, District of Columbia, USA.

Document Type

Journal Article

Publication Date

7-1-2024

Journal

Physiological reports

Volume

12

Issue

13

DOI

10.14814/phy2.16110

Keywords

CIH; autonomic imbalance; cardiac miRNA expression; cardiac remodeling; chronic intermittent hypoxia; transcription

Abstract

Pediatric obstructive sleep apnea poses a significant health risk, with potential long-term consequences on cardiovascular health. This study explores the dichotomous nature of neonatal cardiac response to chronic intermittent hypoxia (CIH) between males and females, aiming to fill a critical knowledge gap in the understanding of sex-specific cardiovascular consequences of sleep apnea in early life. Neonates were exposed to CIH until p28 and underwent comprehensive in vivo physiological assessments, including whole-body plethysmography, treadmill stress-tests, and echocardiography. Results indicated that male CIH rats weighed 13.7% less than age-matched control males (p = 0.0365), while females exhibited a mild yet significant increased respiratory drive during sleep (93.94 ± 0.84 vs. 95.31 ± 0.81;p = 0.02). Transcriptomic analysis of left ventricular tissue revealed a substantial sex-based difference in the cardiac response to CIH, with males demonstrating a more pronounced alteration in gene expression compared to females (5986 vs. 3174 genes). The dysregulated miRNAs in males target metabolic genes, potentially predisposing the heart to altered metabolism and substrate utilization. Furthermore, CIH in males was associated with thinner left ventricular walls and dysregulation of genes involved in the cardiac action potential, possibly predisposing males to CIH-related arrhythmia. These findings emphasize the importance of considering sex-specific responses in understanding the cardiovascular implications of pediatric sleep apnea.

Department

Pharmacology and Physiology

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