Monocyte-derived and CD34+KDR+ endothelial progenitor cells in heart failure.

Background: Endothelial progenitor cells(EPCs) are known to be altered in HF whilst monocyte-derived EPCs in HF have not been assessed. We aimed to characterise monocyte-derived endothelial progenitor cells(EPC) in systolic heart failure(HF). Methods and results: We recruited 128 subjects with systolic HF: 50 South Asian(SA), 50 White, and 28 African-Caribbean(AC) for inter-ethnic comparisons. Additionally, SAs with HF were compared to 40 SAs with CAD without HF ('disease controls', DC) and 40 SA healthy controls(HC). Counts of CD34+ and KDR+ monocytes attributed to specific monocyte subsets (CD14++CD16-[Mon1], CD14++CD16+[Mon2], and CD14+CD16++[Mon3]) and monocyte expression of VEGF receptor 1 were analysed by flow cytometry. We also enumerated CD34+KDR+ EPCs derived from mononuclear cells ('classical' EPC definition). Results: SAs with HF had significantly reduced counts of CD34+ monocytes, attributed to Mon1 and Mon2 subsets. KDR+ Mon1 were 4.5-fold increased in DC compared with HC, but significantly reduced in HF vs. DC. VEGF receptor 1 expression on Mon1 and Mon2 was significantly reduced in HF compared to DC. Also, CD34+KDR+ EPCs were reduced in HF subjects. Whites had significantly less KDR-expressing Mon3 than AC, but significantly more CD34-expressing Mon2 than SA and AC. VEGF receptor 1 expression by Mon1 monocytes was predictive for left ventricular ejection fraction after adjustment for ethnicity (β=-0.25. p=0.039). Counts of CD34+ Mon2 correlated with measures of microvascular endothelial function and were predictive of the future risk hospital admissions. Conclusion: Circulating counts of monocyte-derived EPCs are significantly altered in HF, with significant ethnic differences in the levels of monocyte-derived EPCs. © 2012 International Society on Thrombosis and Haemostasis.