Personalized cytomic assessment of vascular health: Evaluation of the vascular health profile in diabetes mellitus

Authors

  • Nicholas Kurtzman,

    1. Department of Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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    • Nicholas Kurtzman and Lifeng Zhang contributed equally to this work.

  • Lifeng Zhang,

    1. Department of Medicine, Division of Cardiovascular Disease, Section of Vascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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    • Nicholas Kurtzman and Lifeng Zhang contributed equally to this work.

  • Benjamin French,

    1. Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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  • Rebecca Jonas,

    1. Department of Medicine, Division of Cardiovascular Disease, Section of Vascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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  • Andrew Bantly,

    1. Department of Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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  • Wade T. Rogers,

    1. Department of Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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  • Jonni S. Moore,

    1. Department of Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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  • Michael R. Rickels,

    1. Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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  • Emile R. Mohler III

    Corresponding author
    1. Department of Medicine, Division of Cardiovascular Disease, Section of Vascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
    • Department of Pathology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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Correspondence to: Emile R. Mohler III, MD, University of Pennsylvania, Translational Research Center Mail Stop 5159, 3400 Civic Center Blvd, Bldg 421, Room 11-103, Philadelphia 19104-5159, PA, USA. E-mail: mohlere@uphs.upenn.edu

Abstract

Background

An inexpensive and accurate blood test does not currently exist that can evaluate the cardiovascular health of a patient. This study evaluated a novel high dimensional flow cytometry approach in combination with cytometric fingerprinting (CF), to comprehensively enumerate differentially expressed subsets of pro-angiogenic circulating progenitor cells (CPCs), involved in the repair of vasculature, and microparticles (MPs), frequently involved in inflammation and thrombosis. CF enabled discovery of a unique pattern, involving both MPs and CPCs and generated a personalized signature of vascular health, the vascular health profile (VHP).

Methods

Levels of CPCs and MPs were measured with a broad panel of cell surface markers in a population with atherosclerosis and type 2 diabetes mellitus (DM) and age-similar Healthy controls (HC) using an unbiased computational approach, termed CF.

Results

Circulating hematopoietic stem and progenitor cell (CHSPCAng) levels were detected at significantly lower concentrations in DM (P < 0.001), whereas levels of seven phenotypically distinct MPs were present at significantly higher concentrations in DM patients and one MP subset was present at significantly lower concentration in DM patients. Collectively, the combination of CHSPCAng and MP levels was more informative than any one measure alone.

Conclusions

This work provides the basis for a personalized cytomic vascular health profile that may be useful for a variety of applications including drug development, clinical risk assessment and companion diagnostics. © 2013 International Clinical Cytometry Society

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