Endothelial progenitor cells mobilization after maximal exercise according to heart failure severity

Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure (CHF). Patients with CHF are characterized by impaired vasodilation and inflammation of the vascular endothelium. They also have low levels of endothelial progenitor cells (EPCs). EPCs are bone marrow derived cells involved in endothelium regeneration, homeostasis, and neovascularization. Exercise has been shown to improve vasodilation and stimulate the mobilization of EPCs in healthy people and patients with cardiovascular comorbidities. However, the effects of exercise on EPCs in different stages of CHF remain under investigation.

To evaluate the effect of a symptom-limited maximal cardiopulmonary exercise testing (CPET) on EPCs in CHF patients of different severity.

Forty-nine consecutive patients (41 males) with stable CHF [mean age (years): 56 ± 10, ejection fraction (EF, %): 32 ± 8, peak oxygen uptake (VO₂, mL/kg/min): 18.1 ± 4.4] underwent a CPET on a cycle ergometer. Venous blood was sampled before and after CPET. Five circulating endothelial populations were quantified by flow cytometry: Three subgroups of EPCs [CD34⁺/CD45^-/CD133⁺, CD34⁺/CD45^-/CD133⁺/VEGFR₂ and CD34⁺/CD133⁺/vascular endothelial growth factor receptor 2 (VEGFR₂)] and two subgroups of circulating endothelial cells (CD34⁺/CD45^-/CD133^- and CD34⁺/CD45^-/CD133^-/VEGFR₂). Patients were divided in two groups of severity according to the median value of peak VO₂ (18.0 mL/kg/min), predicted peak VO₂ (65.5%), ventilation/carbon dioxide output slope (32.5) and EF (reduced and mid-ranged EF). EPCs values are expressed as median (25th-75th percentiles) in cells/10⁶ enucleated cells.

Patients with lower peak VO₂ increased the mobilization of CD34⁺/CD45^-/CD133⁺ [pre CPET: 60 (25-76) vs post CPET: 90 (70-103) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD45^-/CD133⁺/VEGFR₂ [pre CPET: 1 (1-4) vs post CPET: 5 (3-8) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD45^-/CD133^- [pre CPET: 186 (141-361) vs post CPET: 488 (247-658) cells/10⁶ enucleated cells, P < 0.001] and CD34⁺/CD45^-/CD133^-/VEGFR₂ [pre CPET: 2 (1-2) vs post CPET: 3 (2-5) cells/10⁶ enucleated cells, P < 0.001], while patients with higher VO₂ increased the mobilization of CD34⁺/CD45^-/CD133⁺ [pre CPET: 42 (19-73) vs post CPET: 90 (39-118) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD45^-/CD133⁺/VEGFR₂ [pre CPET: 2 (1-3) vs post CPET: 6 (3-9) cells/10⁶ enucleated cells, P < 0.001], CD34⁺/CD133⁺/VEGFR₂ [pre CPET: 10 (7-18) vs post CPET: 14 (10-19) cells/10⁶ enucleated cells, P < 0.01], CD34⁺/CD45^-/CD133^- [pre CPET: 218 (158-247) vs post CPET: 311 (254-569) cells/10⁶ enucleated cells, P < 0.001] and CD34⁺/CD45^-/CD133^-/VEGFR₂ [pre CPET: 1 (1-2) vs post CPET: 4 (2-6) cells/10⁶ enucleated cells, P < 0.001]. A similar increase in the mobilization of at least four out of five cellular populations was observed after maximal exercise within each severity group regarding predicted peak, ventilation/carbon dioxide output slope and EF as well (P < 0.05). However, there were no statistically significant differences in the mobilization of endothelial cellular populations between severity groups in each comparison (P > 0.05).

Our study has shown an increased EPCs and circulating endothelial cells mobilization after maximal exercise in CHF patients, but this increase was not associated with syndrome severity. Further investigation, however, is needed.