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Published on: January 28, 2020
Microfluidic assay of circulating endothelial cells in coronary artery disease patients with angina pectoris
Shuiyu Chen1, Yukun Sun1, Kuang Hong Neoh1
1College of Engineering, Peking University, Beijing, China.
Insights
Circulating endothelial cell (CEC) counts are significantly elevated in coronary artery disease (CAD) patients with angina pectoris. A novel microfluidic assay demonstrates potential for CECs as a clinical biomarker for endothelial dysfunction in CAD.
Area of Science:
- Cardiovascular Research
- Biomarker Discovery
- Microfluidics
Background:
- Circulating endothelial cells (CECs) are recognized biomarkers for endothelial damage in coronary artery disease (CAD).
- Existing quantification methods (immunomagnetic beads, flow cytometry) have limitations including non-specific binding and high variability.
- A novel microfluidic chip was developed to improve CEC harvesting and morphology preservation for CAD assessment.
Purpose of the Study:
- To develop and validate a label-free microfluidic assay for efficient CEC enumeration.
- To assess the diagnostic and prognostic value of CEC counts in CAD patients with angina pectoris.
- To overcome limitations of current CEC quantification techniques.
Main Methods:
- A label-free microfluidic chip with staggered micropillars was utilized for CEC capture.
- In-situ enumeration and immunofluorescent identification (DAPI+/CD146+/VEGFR1+/CD45-) of CECs were performed.
- The assay was tested on 55 CAD patients (16 chronic stable angina, 39 unstable angina) and 15 healthy controls.
Main Results:
- CEC counts were significantly higher in both chronic stable angina (CSA) and unstable angina (UA) groups compared to healthy controls (p < 0.01).
- A dose-dependent increase in CEC counts was observed across UA risk subgroups (p < 0.001).
- Receiver-operating characteristic analysis showed high area under the curve values (0.867 for CSA, 0.938 for UA) for distinguishing patient groups.
Conclusions:
- The developed microfluidic assay is efficient and stable for CEC capture and enumeration.
- CEC counts show significant potential as a clinical biomarker for assessing endothelial damage/dysfunction in CAD patients.
- This method offers a promising alternative for evaluating endothelial health in cardiovascular disease.
Background:
Circulating endothelial cells (CECs) are widely reported as a promising biomarker of endothelial damage/dysfunction in coronary artery disease (CAD). The two popular methods of CEC quantification include the use of immunomagnetic beads separation (IB) and flow cytometry analysis (FC); however, they suffer from two main shortcomings that affect their diagnostic and prognostic responses: non-specific bindings of magnetic beads to non-target cells and a high degree of variability in rare cell identification, respectively. We designed a microfluidic chip with spatially staggered micropillars for the efficient harvesting of CECs with intact cellular morphology in an attempt to revisit the diagnostic goal of CEC counts in CAD patients with angina pectoris.
Methods:
A label-free microfluidic assay that involved an in-situ enumeration and immunofluorescent identification (DAPI+/CD146+/VEGFR1+/CD45-) of CECs was carried out to assess the CEC count in human peripheral blood samples. A total of 55 CAD patients with angina pectoris [16 with chronic stable angina (CSA) and 39 with unstable angina (UA)], together with 15 heathy controls (HCs) were enrolled in the study.
Results:
CEC counts are significantly higher in both CSA and UA groups compared to the HC group [respective medians of 6.9, 10.0 and 1.5 cells/ml (p < 0.01)]. Further, a significant elevation of CEC count was observed in the three UA subgroups [low risk (5.3) vs. intermediate risk (10.8) vs. high risk (18.0) cells/ml, p < 0.001) classified in accordance to the TIMI NSTEMI/UA risk score system. From the receiver-operating characteristic curve analysis, the AUCs for distinguishing CSA and UA from HC were 0.867 and 0.938, respectively. The corresponding sensitivities were 87.5% and 84.6% and the specificities were 66.7% and 86.7%, respectively.
Conclusions:
Our microfluidic assay system is efficient and stable for CEC capture and enumeration. The results showed that the CEC count has the potential to be a promising clinical biomarker for the assessment of endothelial damage/dysfunction in CAD patients with angina pectoris.
