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Circulating endothelial cells as biomarker for cardiovascular diseases
Maura Farinacci1,2,3, Thomas Krahn4, Wilfried Dinh5,6
1Institute for Medical Immunology Charité University of Medicine Berlin Germany.
Insights
A new validated flow cytometry method accurately quantifies circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs). Elevated CEC levels are significant biomarkers for diagnosing diabetic nephropathy and heart failure with preserved ejection fraction.
Area of Science:
- Cardiovascular Research
- Biomarker Discovery
- Flow Cytometry
Background:
- Endothelial dysfunction is implicated in cardiovascular diseases.
- Circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) may serve as diagnostic biomarkers.
- Current methods for quantifying rare CECs and EPCs lack validation.
Purpose of the Study:
- To develop and validate a flow cytometric assay for quantifying CECs and EPCs in human whole blood.
- To assess the clinical utility of CECs and EPCs as biomarkers for endothelial dysfunction.
Main Methods:
- Optimized assay sensitivity, robustness, and sample storage for clinical application.
- Analyzed CECs and EPCs in patients with heart failure (HFpEF, HFrEF), arterial hypertension (aHT), and diabetic nephropathy (DN) versus healthy controls.
Main Results:
- The developed assay demonstrated high sensitivity and reproducibility.
- Significantly elevated CEC levels were observed in patients with DN and HFpEF compared to controls.
- CEC quantification achieved 90% diagnostic sensitivity for DN and notable sensitivity for HFpEF and aHT.
Conclusions:
- A robust and precise assay for quantifying CECs and EPCs has been established for clinical and pre-clinical use.
- CEC counts are a valuable diagnostic biomarker for diabetic nephropathy and heart failure with preserved ejection fraction.
Background:
Endothelial dysfunction is involved in several cardiovascular diseases. Elevated levels of circulating endothelial cells (CECs) and low levels of endothelial progenitor cells (EPCs) have been described in different cardiovascular conditions, suggesting their potential use as diagnostic biomarkers for endothelial dysfunction. Compared to typical peripheral blood leukocyte subsets, CECs and EPCs occur at very low frequency. The reliable identification and characterization of CECs and EPCs is a prerequisite for their clinical use, however, a validated method to this purpose is still missing but a key for rare cell events.
Objectives:
To establish a validated flow cytometric procedure in order to quantify CECs and EPCs in human whole blood.
Methods:
In the establishment phase, the assay sensitivity, robustness, and the sample storage conditions were optimized as prerequisite for clinical use. In a second phase, CECs and EPCs were analyzed in heart failure with preserved (HFpEF) and reduced (HFrEF) ejection fraction, in arterial hypertension (aHT), and in diabetic nephropathy (DN) in comparison to age-matched healthy controls.
Results:
The quantification procedure for CECs and EPCs showed high sensitivity and reproducibility. CEC values resulted significantly increased in patients with DN and HFpEF in comparison to healthy controls. CEC quantification showed a diagnostic sensitivity of 90% and a sensitivity of 68.0%, 70.4%, and 66.7% for DN, HFpEF, and aHT, respectively.
Conclusion:
A robust and precise assay to quantify CECs and EPCs in pre-clinical and clinical studies has been established. CEC counts resulted to be a good diagnostic biomarker for DN and HFpEF.
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