Mitochondrial respiration and oxidative stress in congenital heart disease

Abstract

Introduction

Cardiopulmonary exercise test (CPET) is the key examination in the follow-up of congenital heart disease (CHD), reflecting aerobic metabolism leading to ATP production by mitochondria. Peripheral blood mononuclear cells (PBMCs) and mitochondrial respiration is related to the severity of acquired heart disease and heart failure.

Objective

To assess PBMC's mitochondrial respiration in patients with CHD and investigate its correlation with CPET and echocardiographic parameters.

Methods

Peripheral blood sample withdrawal were obtained from 26 adult patients with CHD: tetralogy of Fallot (TOF, n = 10), transposition of great arteries (TGA, n = 6) and left sided obstructive lesions (LSOLs, n = 10) as part of their routine blood tests. Healthy volunteers (n = 15, matched for sex and age) were also recruited. Blood samples were tested for mitochondrial respiration (using the Oroboros Oxygraph system) and production of reactive oxygen species (ROS). CPET and echocardiography were performed the same day.

Expected results

We aim to understand how the energetic metabolism is linked with the functional status of patients with CHD.

Based on previous studies, we expect to observe impairments in mitochondrial respiration and increased oxidative stress proportional to the gravity of the cardiopathy and the alteration of the CPET.

Preliminary results show a declining trend of the coupling efficiency (or RCR, ratio of mitochondrial respiration) in oxidative phosphorylation compared to healthy controls, notably in ToF group (P = 0.03) (Fig. 1). Surprisingly we did not observe any significant differences in production of ROS (Fig. 1).

Work is in ongoing to establish a strong statistical correlation with clinical data, primarily with the severity of the CHD.

Perspectives

Exploring energetic metabolism could be a useful non-invasive complementary tool in evaluating the severity of CHD. Further studies, with larger effectives, may confirm these values as reliable biomarkers for prognosis or support other clinical assessments. Finally, mitochondrial modulation could become a new therapeutic target.