Effect of targeted therapy on circulating progenitor cells in precapillary pulmonary hypertension

Int J Cardiol. 2017 Feb 1:228:238-243. doi: 10.1016/j.ijcard.2016.11.175. Epub 2016 Nov 9.


Background: Endothelial dysfunction is key in the development of pulmonary hypertension (PH) and is associated with reduced number of circulating progenitor cells. Studies to date evaluating levels of circulating progenitor cells in PH have provided conflicting results. Current treatment of pulmonary arterial hypertension (PAH) and medical treatment of chronic thromboembolic pulmonary hypertension (CTEPH) targets endothelium dependent signalling pathways. The effect of PAH-targeted therapy on circulating progenitor cells has not been clearly established.

Objectives: To investigate whether levels of circulating progenitor cells in treatment-naïve patients with PAH or CTEPH differ from healthy subjects and to assess the effect of PAH-targeted therapy on the circulating levels of these progenitors.

Methods: Thirty controls, 33 PAH and 11 CTEPH treatment-naïve patients were studied. Eighteen patients with PAH and 9 with CTEPH were re-evaluated 6-12months after starting PAH-targeted therapy. Levels of progenitors were measured by flow cytometry as CD45+CD34+ and CD45+CD34+CD133+ cells.

Results: Compared with controls, the number of circulating progenitor cells was reduced in PAH but not in CTEPH. After 6-12months of treatment, levels of circulating progenitors increased in PAH and remained unchanged in CTEPH. Patients with lower exercise tolerance presented lower levels of circulating progenitors. No other relation was found between levels of progenitors and clinical or hemodynamic parameters.

Conclusions: Patients with PAH, but not those with CTEPH, present reduced levels of circulating progenitor cells. PAH-targeted therapy increases levels of progenitors in PAH but not in CTEPH, suggesting different involvement of progenitor cells in the pathobiology of these pulmonary hypertensive disorders.

Keywords: Circulating progenitor cells; PAH-targeted therapy; Treatment-naïve patients.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Cell Count
  • Chronic Disease
  • Cross-Sectional Studies
  • Female
  • Humans
  • Hypertension, Pulmonary / blood*
  • Hypertension, Pulmonary / physiopathology
  • Hypertension, Pulmonary / therapy
  • Male
  • Middle Aged
  • Pulmonary Embolism / blood*
  • Pulmonary Embolism / physiopathology
  • Pulmonary Embolism / therapy
  • Stem Cells*