Chronic heart failure is characterized by altered mitochondrial function and structure in circulating leucocytes

Abstract

Oxidative stress is currently viewed as a key factor in the genesis and progression of Heart Failure (HF). The aim of this study was to characterize the mitochondrial changes linked to oxidative stress generation in circulating peripheral blood mononuclear cells isolated from chronic HF patients (HF_PBMCs) in order to highlight the involvement of mitochondrial dysfunction in the pathophysiology of HF.To assess the production of reactive oxygen species (ROS), mitochondrial function and ultrastructure and the mitophagic flux in circulating PBMCs we enrolled 15 patients with HF and a control group of ten healthy subjects. The HF_PBMCs showed a mitochondrial population consisting of damaged and less functional organelles responsible of higher superoxide anion production both at baseline and under in vitro stress conditions, with evidence of cellular apoptosis. Although the mitophagic flux at baseline was enhanced in HF_PBMCs at level similar to those that could be achieved in control PBMCs only under inflammatory stress conditions, the activation of mitophagy was unable to preserve a proper mitochondrial dynamics upon stress stimuli in HF.In summary, circulating HF_PBMCs show structural and functional derangements of mitochondria with overproduction of reactive oxidant species. This mitochondrial failure sustains a leucocyte dysfunctional status in the blood that may contribute to development and persistence of stress conditions within the cardiovascular system in HF.

Peripheral Blood Mononuclear Cells and Platelets Mitochondrial Dysfunction, Oxidative Stress, and Circulating mtDNA in Cardiovascular Diseases

“…Song et al found lower MTP and higher ROS levels in lymphocytes of CHF patients at low risk associated with increased serum NT-ProBNP, a diagnosis and prognosis biomarker in heart failure [36]. Furthermore, Coluccia et al, analyzing the mitochondrial membrane potential by cytofluorometric TMRM and JC-1 staining, found significant mitochondrial depolarization in PBMCs among HF patients after the administration of inflammatory stimulus lipopolysaccharide (LPS) [38]. The ultrastructural changes in mitochondria PBMCs showed a decrease in the index associated with the loss of inner mitochondrial membrane (IMM) and with an increase in the percentage of the apoptotic cells and mitophagy in HF-PBMC individuals, both at baseline and after LPS stimulation.…”

“…The ultrastructural changes in mitochondria PBMCs showed a decrease in the index associated with the loss of inner mitochondrial membrane (IMM) and with an increase in the percentage of the apoptotic cells and mitophagy in HF-PBMC individuals, both at baseline and after LPS stimulation. The impairment of the inner mitochondrial membrane in PBMCs might reflect the impairment of the electron transport chain mitochondrial uncoupling [38] (Table 1). Thus, PBMCs' mitochondrial respiration can be considered as an innovative model to investigate the pathophysiology of CVDs.…”

“…Indeed, high levels of ROS and increased production of superoxide anion by neutrophils have been observed in the blood of HF patients, and white blood cells and platelets producing ROS can amplify oxidative stress and organ damage in HF [48,65]. A recent study showed that circulating PBMCs present structural and functional derangements of mitochondria with overproduction of ROS in HF [38]. Besides, a significant reduction of respiration was associated with a higher mitochondrial ROS production in PBMCs of patients with moderate to severe CHF compared to mild CHF [22].…”

Endostatin attenuates heart failure via inhibiting reactive oxygen species in myocardial infarction rats

“…Reactive oxygen species (ROS) generated during cellular aerobic respiration and metabolism are implicated in cardiovascular diseases [16,17]. Peripheral blood mononuclear cells isolated from chronic HF patients show a mitochondrial population consisting of damaged and less functional organelles, which is responsible for higher superoxide anion production [18]. Endostatin treatment significantly decreases prostate cancer cell proliferation Downloaded from http://portlandpress.com/bioscirep/article-pdf/doi/10.1042/BSR20200787/888525/bsr-2020-0787.pdf by guest on 03 November 2020 through up-regulation of manganese superoxide dismutase and the reduced glutathione [19].…”

Mitochondrial Function in Peripheral Blood Mononuclear Cells (PBMC) Is Enhanced, Together with Increased Reactive Oxygen Species, in Severe Asthmatic Patients in Exacerbation

“…Besides this local characterization of the asthma mechanism, there are relatively few data focused on a potential involvement of mitochondrial function of inflammatory circulatory cells. However, dysfunction of the mitochondrial respiratory chain is likely to play a role in the initiation and progression of other inflammatory pathology such as cardiovascular diseases and anaphylactic choc [17,18,19,20]. Furthermore, impairments in mitochondrial function and/or elevation of ROS production have been found in allergic diseases such as atopy, atopic dermatitis and allergic rhinitis [3,4,21,22].…”