Inhibition of Cyclophilin D Rescues Cardiac Function and Bioenergetic Defects Caused by Neonatal Hypoxia

JACC Basic to Translational Science 2026 Open access

Read full text
Authors: Jonathan R Burris, Gisela Beutner, Min Yee, Bartholomew V. Simon, Michael F. Swartz, Kathryn B. Boudreau, Ethan David Cohen, Chaitanya A. Kulkarni, Prottoy Hasan, Hongyue Wang, Karen L. de Mesy Bentley, György Hajnóczky
+5 more George M. Alfieris, Eric M. Small, Paul S. Brookes, Michael A. O’Reilly, George Arthur Porter Jr.
DOI: 10.1016/j.jacbts.2026.101544
Cited by: 1
References: 56

Abstract

Increased oxygen levels at birth regulate myocyte bioenergetic and structural maturation controlled by mitochondrial cyclophilin D (CypD). We evaluated mechanisms of neonatal hypoxic cardiac dysfunction by exposing neonatal mice to 12% oxygen and studied cardiac bioenergetics, myocyte maturation, and function. Hypoxia decreased the activity/assembly of electron transport chain complex I, uncoupled oxidative phosphorylation, increased proliferation, decreased differentiation, increased ventricular mass, and decreased cardiac function. CypD inhibition rescued most hypoxia-mediated effects and increased cardiac function. In conclusion, neonatal hypoxia alters cardiac bioenergetics, myocyte maturation, and cardiac function through CypD-dependent pathways, providing potential therapeutic targets for neonatal cardiac dysfunction.

Fields of Study & Subjects

Signaling Pathways in Disease GDF15 and Related Biomarkers Blood Coagulation and Thrombosis Mechanisms

Publication details

Journal / source
JACC Basic to Translational Science
Publisher
Elsevier BV
Volume
11
Issue
5
Pages
101544–101544
Publication date
24 April 2026
Language
EN