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.
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.
