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Circulating cells as predictors of secondary manifestations of cardiovascular disease: design of the CIRCULATING CELLS study

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Abstract

Biomarkers for primary or secondary risk prediction of cardiovascular disease (CVD) are urgently needed to improve individual treatment and clinical trial design. The vast majority of biomarker discovery studies has concentrated on plasma/serum as an easily accessible source. Although numerous markers have been identified, their added predictive value on top of traditional risk factors has been limited, as the biological specimen does not specifically reflect expression profiles related with CVD progression and because the signal is often diluted by marker release from other organs. In contrast to serum markers, circulating cells serve as indicators of the actual disease state due to their active role in the pathogenesis of CVD and are responsible for the majority of secreted biomarkers. Therefore, the CIRCULATING CELLS study was initiated, focusing on the cellular effectors of atherosclerosis in the circulation. In total, 714 patients with coronary artery disease (CAD) symptoms were included. Blood cell fractions (monocytes, T-lymphocytes, platelets, granulocytes, PBMC) of all individual patients were isolated and stored for analysis. Concomitantly, extensive flow cytometric characterization of these populations was performed. From each patient, a detailed clinical profile together with extensive questionnaires about medical history and life style was obtained. Various high-throughput -omics approaches (protein, mRNA, miRNA) are currently being undertaken. Data will be integrated with advanced bioinformatics for discovery and validation of secondary risk markers for adverse events. Overall, the CIRCULATING CELLS study grants the interesting possibility that it will both identify novel biomarkers and provide useful insights into the pathophysiology of CAD in patients.

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Acknowledgments

This research was performed within the framework of CTMM, the Center for Translational Molecular Medicine (www.ctmm.nl), project CIRCULATING CELLS (grant 01C-102), and supported by the Dutch Heart Foundation

Conflict of interest

None declared

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Authors and Affiliations

  1. Laboratory of Experimental Cardiology, UMC Utrecht, Room G02.523, Heidelberglaan 100, 3584, Utrecht, CX, The Netherlands

    Imo E. Hoefer, Marieke Hillaert & Gerard Pasterkamp

  2. Department of Cardiology, Catharina Ziekenhuis Eindhoven, Eindhoven, The Netherlands

    Jan-Willem Sels & Nico Pijls

  3. Department of Cardiology, Leiden UMC, Leiden, The Netherlands

    J. Wouter Jukema & Sandrin Bergheanu

  4. Department of Pathology, Maastricht UMC, Maastricht, The Netherlands

    Erik Biessen

  5. Department of Bioinformatics, Erasmus University Medical Center, Rotterdam, The Netherlands

    Elizabeth McClellan, Sebastiaan Horsman, Peter van der Spek & Andrew Stubbs

  6. Department of Pathology, AMC Amsterdam, Amsterdam, The Netherlands

    Mat Daemen

  7. Department of Cardiology, UMC Utrecht, Utrecht, The Netherlands

    Pieter Doevendans & Marieke Hillaert

  8. Department of Hematology, UMC Utrecht, Utrecht, The Netherlands

    Philip de Groot

  9. Department of Cardiology, Maastricht UMC, Maastricht, The Netherlands

    Mustafa Ilhan & Johannes Waltenberger

  10. Department of Biopharmaceutics, Leiden University, Leiden, The Netherlands

    Johan Kuiper

  11. Institute for Medical Technology Assessment, Erasmus University Rotterdam, Rotterdam, The Netherlands

    Ken Redekop

  12. Department of Nephrology, Leiden UMC, Leiden, The Netherlands

    Eric van de Veer & Anton-Jan van Zonneveld

  13. The Einthoven Laboratory for Experimental Vascular Medicine, Leiden UMC, Leiden, The Netherlands

    Eric van de Veer & Anton-Jan van Zonneveld

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  1. Imo E. Hoefer
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  2. Jan-Willem Sels
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Correspondence to Imo E. Hoefer.

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Hoefer, I.E., Sels, JW., Jukema, J.W. et al. Circulating cells as predictors of secondary manifestations of cardiovascular disease: design of the CIRCULATING CELLS study. Clin Res Cardiol 102, 847–856 (2013). https://doi.org/10.1007/s00392-013-0607-9

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