Heart failure with preserved ejection fraction (HFpEF) is a common clinical entity, with no effective treatment shown to reduce morbidity and mortality. Endothelial progenitor cells (EPC) are bone marrow derived circulating cells able to proliferate and differentiate into functional mature endothelial cells. EPCs are mobilized into the circulation in response to tissue or vessel injury and participate in the process of endothelial surface repair. EPCs co-express CD133, CD34 and VEGFR-2 antigens on their surface. Given the potential role of the microvascular endothelium in the pathogenesis of HFpEF, we hypothesized that the level and function of EPCs may be attenuated in this condition. Accordingly, the aim of the study was to compare the level and function of EPCs in patients with HFpEF compared with HFrEF and control subjects.
Methods
We enrolled 21 patients with HFpEF (LVEF>50% by echocardiography), 11 patients with HFrEF (LVEF<40%) and 11 healthy controls. Circulating EPC levels were quantified by expression of VEGFR-2, CD34 and CD133 by flow cytometry (expressed as percentage of PMNCs co-expressing VEGFR-2 and CD133, or VEGFR-2 and CD34). EPCs colony forming units (CFUs) were counted after 7 days in culture.
Results
EPC levels and EPC-CFU in the HFpEF group (mean age 74.5 years, 57% women, 48% with DM), HFrEF group (mean age 68.1 years, 9% women and 64% with DM) and the control group (mean age 53.3 years, 9% women and 64% with DM), are presented in the Table.
HFrEF (n=11) |
HFpEF (n=21) |
CONTROL (n=11) |
P value HFrEF VS. CONTROL |
P value HFpEF VS. CONTROL |
|
CD34+/VEGFR2+ |
0.44±0.37
|
0.37±0.26
|
0.89±0.68 |
0.05 |
0.004 |
CD133+/VEGFR2+ |
0.13±0.06 |
0.15±0.16 |
0.50±0.46 |
0.01 |
0.002 |
CFU |
16.29±14.57 |
12.43±18.47 |
44.27±29.85 |
0.03 |
0.005 |
Conclusion
Our data demonstrate for the first time that both circulating EPC levels, and CFUs are significantly lower in both patients with preserved and reduced heart failure compared with healthy controls.