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

Abstract

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. © 2012 International Society on Thrombosis and Haemostasis.