Peripheral Blood Mononuclear Cells Mitochondrial Respiration and Superoxide Anion after Heart Transplantation

Abstract

Introduction: The mitochondrial function of circulating peripheral blood mononuclear cells (PBMCs) is an interesting new approach to cardiac diseases. Thus, PBMC’s mitochondrial respiration decreases in relation to heart failure severity. However, no data are available on heart-transplanted patients (Htx). Population and Methods: We determined PBMCs mitochondrial respiration by high-resolution respirometry (Oroboros Instruments) and superoxide anion production using electron paramagnetic resonance (Bruker-Biospin) in 20 healthy subjects and 20 matched Htx and investigated clinical, biological, echocardiographic, coronarography and biopsy characteristics. Results: PBMCs mitochondrial respiratory chain complex II respiration was decreased in Htx (4.69 ± 0.84 vs. 7.69 ± 1.00 pmol/s/million cell in controls and Htx patients, respectively; p = 0.007) and complex IV respiration was increased (24.58 ± 2.57 vs. 15.68 ± 1.67 pmol/s/million cell; p = 0.0035). Superoxide anion production was also increased in Htx (1.47 ± 0.10 vs. 1.15 ± 0.10 µmol/min; p = 0.041). The leucocyte-to-lymphocyte ratio was increased in Htx, whom complex II correlated with leucocyte number (r = 0.51, p = 0.02) and with the left ventricular posterior wall peak early diastolic myocardial velocity (r = −0.62, p = 0.005). Complex IV was increased in the two patients with acute rejection and correlated negatively with Htx’s isovolumetric relation time (r = −0.45, p = 0.045). Discussion: Although presenting with normal systolic function, Htx demonstrated abnormal PBMC’s mitochondrial respiration. Unlike immunosuppressive therapies, subclinical diastolic dysfunction might be involved in these changes. Additionally, lymphopenia might reduce complex II, and acute rejection enhances complex IV respirations. Conclusion: PBMC’s mitochondrial respiration appears modified in Htx, potentially linked to cellular shift, mild diastolic dysfunction and/or acute rejection.

Endurance training increases mitochondrial myoglobin and enhances its interaction with complex IV in rat plantaris muscle

“…46 Furthermore, another study has reported that heart transplantation increased complex IV-dependent respiration but not complex I-dependent respiration in human peripheral blood mononuclear cells. 47 These previous studies at least indicate that complex I-dependent respiration may not change regardless of increased complex IV-dependent respiration. Therefore, we believe that the results of the present study do not appear strange.…”

“…Nevertheless, there is a previous study reporting that antioxidant treatment (mitochondrial antioxidant MitoQ) increases complex IV‐dependent respiration but not complex I‐dependent respiration in placentae of male offspring rat 46 . Furthermore, another study has reported that heart transplantation increased complex IV‐dependent respiration but not complex I‐dependent respiration in human peripheral blood mononuclear cells 47 . These previous studies at least indicate that complex I‐dependent respiration may not change regardless of increased complex IV‐dependent respiration.…”