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Abstract 15615: Reactive Oxygen Species Accumulation and Mitochondrial Dysfunction in Peripheral Blood Mononuclear Cells Are Associated With Heart Failure in Patients With Single Ventricle Congenital Heart Disease

Authors :
Garcia, Anastacia M
Sparagna, Genevieve C
Phillips, Elisabeth K
Miyano, Carissa A
Nunley, Karin
Chatfield, Kathryn C
Stauffer, Brian L
Sucharov, Carmen
Miyamoto, Shelley D
Source :
Circulation (Ovid); November 2019, Vol. 140 Issue: Supplement 1 pA15615-A15615, 1p
Publication Year :
2019

Abstract

Introduction:Heart failure (HF) remains a leading cause of death and indication for transplant in children with single ventricle congenital heart disease (SV). However, little is known regarding the molecular mechanisms leading to remodeling and HF in SV. The purpose of this study was to evaluate reactive oxygen species (ROS) and mitochondrial function in circulating peripheral blood mononuclear cells (PBMCs) from pediatric SV patients compared to non-failing controls (NF). Ex vivohigh-resolution respirometry analysis was also conducted on permeabilized myocardial fibers in SV patients who underwent cardiac transplant to determine whether PBMCs may serve as a proxy for tissue-specific cellular respiration.Methods:PBMCs were isolated from whole blood (EDTA) using density gradient centrifugation in Histopaque Accuspin tubes. Oxygen consumption rates (OCR) of intact PBMCs was measured using the Seahorse XFe Bioanalyzer (Agilent). Respiration of explanted myocardial mitochondria was measured using an Oroboros Oxygraph system. ROS (hydrogen peroxide and superoxide) were quantified using Amplex Red dye.Results:ROS was increased (n=5 NF, n=2 SV; p=0.005), while respiratory capacity, coupling efficiency and mitochondrial oxysgen flux were decreased in SV PBMCs relative to NF controls (Figure, n=3 NF, n=2 SV). Moreover, an association between SV PBMC and SV myocardial mitochondrial function was observed (n=2).Conclusions:Our results provide new insights into SV HF by identifying abnormalities in mitochondrial respiratory capacity and ROS accumulation in circulating PBMCs of pediatric SV patients relative to NF controls. Positive associations between SV PBMC and myocardial findings suggest that PBMCs may be a surrogate for myocardial mitochondrial function. Together, these data support mitochondria as a potential therapeutic target in SV HF and suggest that PBMCs could serve as a novel biomarker of HF and response to therapy in the SV population.

Details

Language :
English
ISSN :
00097322 and 15244539
Volume :
140
Issue :
Supplement 1
Database :
Supplemental Index
Journal :
Circulation (Ovid)
Publication Type :
Periodical
Accession number :
ejs59730745
Full Text :
https://doi.org/10.1161/circ.140.suppl_1.15615