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Monocyte‐derived and CD34 + /KDR + endothelial progenitor cells in heart failure
Author(s) -
SHANTSILA E.,
WRIGLEY B. J.,
SHANTSILA A.,
TAPP L. D.,
GILL P. S.,
LIP G. Y. H.
Publication year - 2012
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2012.04753.x
Subject(s) - cd14 , cd34 , medicine , monocyte , kinase insert domain receptor , progenitor cell , endothelial progenitor cell , cd16 , peripheral blood mononuclear cell , heart failure , vascular endothelial growth factor , endocrinology , receptor , immunology , vascular endothelial growth factor a , biology , stem cell , antigen , microbiology and biotechnology , vegf receptors , cd8 , in vitro , biochemistry , cd3
Summary. 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.