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  • Clinical Research
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Circulating white blood cells and platelets amplify oxidative stress in heart failure

Nature Clinical Practice Cardiovascular Medicine volume 5, pages 811–820 (2008)Cite this article

Abstract

Background Mitochondria of circulating white blood cells (WBC) and platelets sense oxidative stress during capillary passage and react by producing reactive oxygen species (ROS). Although evidence indicates that congestive heart failure (CHF) is associated with oxidative stress, the role of WBC and platelets as mediators in CHF has not been investigated.

Methods Patients with CHF (n = 15) and healthy volunteers (n = 9) were enrolled between 2006 and 2007 into this observational study. Arterial and venous blood samples from participants were incubated with probes to detect cytosolic and mitochondrial ROS. Fluorescence-activated cell sorting was used to measure the degree of fluorescence in WBC and platelets.

Results Patients with CHF had a higher proportion of ROS-positive arterial WBC and platelets than did controls (67% ± 47% versus 16% ± 9%; P <0.005), as well as venous WBC and platelets (77% ± 43% versus 38% ± 13%; P <0.01). In the control group, the proportion of cytosolic ROS-positive arterial WBC and platelets was lower than that for ROS-positive venous WBC and platelets (16% ± 9% versus 38% ± 13%; P <0.005). CHF patients had a higher proportion of mitochondrial ROS-positive arterial and venous WBC and platelets than did controls.

Conclusion In CHF, the proportion of WBC and platelets that are ROS-positive is raised, possibly because cytosolic ROS-positive WBC and platelets are normally cleared in the lungs; this function is deficient in CHF while mitochondrial ROS production is increased. The raised numbers of circulating ROS-positive WBC and platelets amplify oxidative stress in CHF.

Key Points

  • In CHF, the proportion of WBC and platelets that are ROS-positive is raised in the cytosol

  • In CHF, WBC and platelets have more ROS-producing mitochondria

  • Oxidative stress is amplified in CHF because of mitochondrial production of ROS in WBC and platelets

  • Oxidative stress is amplified in CHF because of absent pulmonary clearance of ROS-loaded WBC and platelets

  • Pulmonary removal of ROS and transfer of redox active molecules to the mitochondria are new potential targets for CHF therapy

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Figure 1: Study design.
Figure 2: Live-cell microscopy of the leukocyte-rich buffycoat.
Figure 3: Cytoplasmic oxidative stress.
Figure 4: Coronary sinus sampling.
Figure 5: Mitochondrial oxidative stress.
Figure 6: Protein oxidative stress modification.
Figure 7: Circulating white blood cells and platelets amplify oxidative stress in heart failure.

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Authors and Affiliations

  1. Department of Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands

    Alexander JJ IJsselmuiden, Gijsbert de Ruiter & Loek van Heerebeek

  2. Department of Physiology, VU University Medical Centre, Amsterdam, The Netherlands

    René JP Musters, Geert-Jan Tangelder & Walter J Paulus

  3. Department of Hematology and Chemistry, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands

    Frans Alderse-Baas, Muriel van Schilfgaarde & Anja Leyte

  4. Department of Cardiology, King's College Hospital, London, United Kingdom

    Gerrit J Laarman

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Correspondence to Walter J Paulus.

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IJsselmuiden, A., Musters, R., de Ruiter, G. et al. Circulating white blood cells and platelets amplify oxidative stress in heart failure. Nat Rev Cardiol 5, 811–820 (2008). https://doi.org/10.1038/ncpcardio1364

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