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.
Highlights
Heart failure (HF) is a clinical syndrome affecting more than 23 millions of patients worldwide with a high associated morbidity and mortality [1]
Our study focused on the characterization of one of the most complex mechanism involved in the pathogenesis of HF, the mitochondrial oxidative stress in tissue and blood [2, 34]
We focused our attention on a selected population of patients with chronic HF in the attempt to exclude any other conditions that could affect the production of oxidative stress
Summary
Heart failure (HF) is a clinical syndrome affecting more than 23 millions of patients worldwide with a high associated morbidity and mortality [1]. Over the last 30 years several improvements in treatments favored survival in these patients but the prognosis remains unsatisfactory. Oxidative stress and chronic inflammation are key factors involved in the pathophysiology of HF [2]. In this context, the role of mitochondrial dysfunction appears to be of increasing importance [3]. Mitochondria are the main source of intracellular ATP. They control cell death and survival by integrating information from multiple signaling pathways [4]. The mitochondrial network exhibits high tissue specificity in relation with the cell functions. Any change of the internal organization of mitochondria could impair cell energetics and, as a consequence, cell function and viability [5]
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