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Altered chemokine receptor profile on circulating leukocytes in human heart failure

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Abstract

Chemokines and their receptors have been implicated in the pathogenesis of different forms of heart failure (HF). We examined CC-and CXC-chemokine receptor expression in fresh peripheral blood leukocyte populations from 24 end-stage HF patients consisting of coronary artery disease (CAD; n=6) and hypertrophic cardiomyopathy (HCM; n=7) or idiopathic dilated cardiomyopathy (IDCM; n=8) or valvular disease (VD; n=3) and compared the data with 18 healthy controls. Levels of CCR1, 2, 3, 4, 5, and 7, and CXCR1, 2, 3, and 4 were measured by flow cytometry, and the expression profile was assessed as molecules of equivalent soluble fluorochrome units as well as frequency (percentage) of CD3+, CD4+, and CD8+ T cells and monocytes or granulocytes. Frequency of CD3+ CXCR4+, CD3+ CXCR1+, and CD3+ CXCR3+ cells was significantly increased in HF patients, whereas only CCR7 and CXCR4 expression levels were elevated on CD3+ cells. Both CD4+ CXCR4+ and CD8+ CXCR4+ cell frequencies were significantly increased irrespective of cardiac disease etiology. Elevated CCR7 expression was less pronounced on CD4+ than CD8+ cells in patients with CAD and IDCM. Expression of CXCR4 on CD8+ cells was upregulated substantially, regardless of the cause of disease. CD8+ CXCR1+ and CD8+ CXCR3+ but not CD4+ CXCR1+ or CD4+ CXCR3+ cells were increased in the HF patients with IDCM and CAD, respectively. Expression of CXCR1 or CXCR3 on both CD4+ and CD8+ cells did not differ in all the groups. For monocytes, frequency of CD14+ CCR1+ and CD14+ CCR2+ cells was significantly decreased in CAD patients, whereas, increase in CD14+ CXCR4+ cell frequency was accompanied with elevated CXCR4 expression. On granulocytes, CXCR1 and CXCR2 receptors were downregulated in all patients, compared with controls. Our results suggest that the altered expression profile of CC- and CXC-chemokine receptors on circulating leukocyte populations involves enhanced activation of the immune system, perhaps as part of the pathogenic mechanisms in HF. Modulation of the chemokine network could offer interesting novel therapeutic modalities for end-stage HF.

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Authors and Affiliations

  1. Department of Cardiothoracic Surgery, Erasmus MC, Rotterdam, The Netherlands

    Petros Athanassopoulos & Ad J. J. C. Bogers

  2. Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

    Petros Athanassopoulos, Leonard M. B. Vaessen & Willem Weimar

  3. Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands

    Aggie H. M. M. Balk

  4. Department of Pharmacology, Erasmus MC, Rotterdam, The Netherlands

    Hari S. Sharma

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  1. Petros Athanassopoulos
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Correspondence to Ad J. J. C. Bogers.

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Athanassopoulos, P., Vaessen, L.M.B., Balk, A.H.M.M. et al. Altered chemokine receptor profile on circulating leukocytes in human heart failure. Cell Biochem Biophys 44, 83–101 (2006). https://doi.org/10.1385/CBB:44:1:083

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