Pathophysiology of Heart Failure: A Role for Peripheral Blood Mononuclear Cells Mitochondrial Dysfunction?

François Sauer,Alain Meyer,Marianne Riou,Samy Talha,Bernard Geny,Emmanuel Andres,Anne-Laure Charles

doi:10.3390/jcm11030741

Abstract

Heart failure (HF) is a leading cause of hospitalization in patients aged more than 65 years and is associated with high mortality rates. A better comprehension of its physiopathology is still needed, and, in addition to neurohormonal systems and sodium glucose co-transporter 2 modulations, recent studies focus on the mitochondrial respiration of peripheral blood circulating cells (PBMCs). Thus, cardiovascular metabolic risk factors and cellular switch with an increased neutrophil/lymphocytes ratio might favor the decreased PBMC mitochondrial respiration observed in relation with HF severity. PBMCs are implicated in the immune system function and mitochondrial dysfunction of PBMC, potentially induced by their passage through a damaged heart and by circulating mitoDAMPs, which can lead to a vicious circle, thus sustaining negative cardiac remodeling during HF. This new approach of HF complex pathophysiology appears to be a promising field of research, and further studies on acute and chronic HF with reduced or preserved LVEF are warranted to better understand whether circulating PBMC mitochondrial function and mitoDAMPs follow-ups in HF patients might show diagnosis, prognosis or therapeutic usefulness.

Highlights

Heart failure (HF) is a clinical syndrome defined by reduced cardiac output and/or elevated intracardiac pressures at rest or during exercise
Sympathetic nervous, renin–angiotensin–aldosterone and cardiac natriuretic system implications are well-known and their inhibition is the cornerstone of chronic HF management, which has been recently implemented with sodium glucose co-transporter 2 modulators, even in HF-preserved ejection fractions (HFpEFs) up to 60% [1,2,3,4,5]
Neutrophils are activated and increased and could facilitate cardiomyocytes’ apoptosis [24], whereas there is a progressive and relative lymphocytopenia due to the inflammation and down-regulation of the immune system [25]. This cellular switch in HF patients could lead to a decrease in global peripheral blood mononuclear cells (PBMCs) mitochondrial respiration, since neutrophils seem to have a minimal contribution to the oxygen consumption rate and cellular bioenergetics, as compared to lymphocytes and monocytes [26]

Summary

Introduction

Heart failure (HF) is a clinical syndrome defined by reduced cardiac output and/or elevated intracardiac pressures at rest or during exercise. The mitochondrial respiratory function of peripheral blood mononuclear cells (PBMCs) (in extenso lymphocytes and monocytes) is available. Whether their mitochondrial dysfunction could be used as a diagnostic, severity and/or prognosis biomarker in cardiovascular diseases is under evaluation, but the major role of mitochondria in cell energy and reactive oxygen species (ROSs) production support such a hypothesis.

Results

Conclusion