Monocyte-derived and CD34+/KDR+ endothelial progenitor cells in heart failure
E Shantsila1, B J Wrigley, A Shantsila
1University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham Primary Care Clinical Sciences, University of Birmingham, Birmingham, UK.
Insights
Monocyte-derived endothelial progenitor cells (EPCs) are altered in heart failure (HF), with significant ethnic variations. Reduced EPC counts in HF patients correlate with disease severity and predict hospital admission risk.
Area of Science:
- Cardiovascular Research
- Cell Biology
- Immunology
Background:
- Endothelial progenitor cells (EPCs) play a crucial role in vascular health.
- EPCs are known to be altered in heart failure (HF).
- Monocyte-derived EPCs in HF have not been previously characterized.
Purpose of the Study:
- To characterize monocyte-derived EPCs in patients with systolic HF.
- To investigate interethnic differences in monocyte-derived EPCs among HF patients.
- To explore the relationship between monocyte-derived EPCs and HF severity.
Main Methods:
- Recruited 128 systolic HF patients (South Asian, White, African-Caribbean) and controls.
- Analyzed monocyte subsets (CD14/CD16) for CD34+ and KDR+ cell counts via flow cytometry.
- Assessed VEGF receptor 1 expression on monocytes and enumerated CD34+/KDR+ EPCs.
Main Results:
- Systolic HF patients showed reduced CD34+ monocytes in Mon1 and Mon2 subsets.
- KDR+ Mon1 counts were reduced in HF compared to disease controls.
- VEGF receptor 1 expression was lower on Mon1/Mon2 cells in HF patients.
- Reduced CD34+/KDR+ EPC numbers were observed in HF subjects.
- Ethnic differences noted in specific monocyte subsets and VEGF receptor 1 expression.
- VEGF receptor 1 expression predicted left ventricular ejection fraction.
- CD34+ Mon2 counts correlated with microvascular function and predicted hospital admission.
Conclusions:
- Circulating monocyte-derived EPC counts are significantly altered in systolic HF.
- Significant ethnic variations exist in monocyte-derived EPC levels in HF.
- Monocyte-derived EPCs represent a potential biomarker for HF severity and prognosis.
Background:
Endothelial progenitor cells (EPCs) are known to be altered in heart failure (HF), but monocyte-derived EPCs in HF have not been assessed. We aimed to characterize monocyte-derived EPCs in systolic HF.
Methods And Results:
We recruited 128 subjects with systolic HF: 50 South Asian (SA), 50 white, and 28 African-Caribbean (AC), for interethnic comparisons. Additionally, SAs with HF were compared with 40 SAs with coronary artery disease (CAD) without HF (disease controls [DCs]) and 40 SA healthy controls (HCs). Counts of CD34(+) and kinase domain receptor (KDR)(+) monocytes attributed to specific monocyte subsets (CD14(++) /CD16(-) [Mon1], CD14(++)/CD16(+) [Mon2], and CD14(+)/CD16(++) [Mon3]) and monocyte expression of vascular endothelial growth factor (VEGF) receptor 1 were analyzed by flow cytometry. We also enumerated CD34(+)/KDR(+) EPCs derived from mononuclear cells ('classic' EPC definition).
Results:
SAs with HF had significantly reduced counts of CD34(+) monocytes, attributed to the Mon1 and Mon2 subsets. KDR(+) Mon1 counts were 4.5-fold increased in DCs as compared with HCs, but significantly reduced in HF subjects vs. DCs. VEGF receptor type 1 expression on Mon1 and Mon2 cells was significantly reduced in HF patients as compared with DCs. Also, CD34(+)/KDR(+) EPC numbers were reduced in HF subjects. Whites had significantly fewer KDR(+) Mon3 cells than ACs, but significantly more CD34(+) Mon2 cells than SAs and ACs. VEGF receptor type 1 expression by Mon1 cells was predictive for left ventricular ejection fraction after adjustment for ethnicity (β = - 0.25. P = 0.039). CD34(+) Mon2 counts correlated with measures of microvascular endothelial function, and were predictive of the future risk of hospital admission.
Conclusions:
Circulating counts of monocyte-derived EPCs are significantly altered in HF, with significant ethnic differences in the levels of monocyte-derived EPCs.
