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

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.

Keywords: PBMC; heart failure; mitochondria; oxidative stress; pathophysiology; peripheral blood mononuclear cell.

Figure 1

A cellular switch with increased neutrophils and reduced lymphocyte counts can lead to a global decrease in PBMC mitochondrial respiration during heart failure. PBMC: peripheral blood mononuclear cell. ADP: adenosine diphosphate. ATP: adenosine triphosphate.

Figure 2

The “proximity theory”: communication between the damaged cardiomyocytes and PBMC in the heart. CaMKII: calmoduline kinase II; MitoDAMPs: mitochondrial damaged-associated molecular patterns; MR: mitochondrial respiration and ROS: reactive oxygen species.

Figure 3

Potential vicious circle and therapeutic options: the alteration of PBMC mitochondria could exacerbate and/or sustain cardiac dysfunction and disease severity. NRLP3: nucleotide-binding, leucine-rich repeat and pyrin-domain-containing 3; PBMC: peripheral blood mononuclear cells and SGLT2i: sodium glucose co-transporter 2 (SGLT2) inhibitors.