Circulating progenitor cells and their interaction with platelets in patients with an acute coronary syndrome

Abstract

CD34⁺ cells expressing KDR (CD34⁺/KDR⁺) represent a small proportion of circulating progenitor cells that have the capacity to interact with platelets and to differentiate into mature endothelial cells, thus contributing to vascular homeostasis and regeneration as well as to re-endothelialization. We investigated the levels of CD34⁺ and CD34⁺/KDR⁺ progenitor cells as well as their interaction with platelets in acute coronary syndrome (ACS) patients before the initiation (baseline) of their treatment with a P2Y₁₂ receptor antagonist, and at 5-days post-treatment (follow-up). Sixty-seven consecutive ACS patients and thirty healthy subjects (controls) participated in the study. On admission, all patients received 325 mg aspirin, followed by 100 mg/day and then were loaded either with 600 mg clopidogrel or 180 mg ticagrelor, followed by 75 mg/day (n = 36) or 90 mg × 2/day (n = 31), respectively. The levels of circulating CD34⁺ and CD34⁺/KDR⁺ progenitor cells, as well as their interaction with platelets, were determined by flow cytometry, before and after activation with ADP, in vitro. The circulating levels of CD34⁺ and CD34⁺/KDR⁺ cells in both patient groups at baseline were lower compared with controls while they were significantly increased at 5-days of follow-up in both groups, this increase being more pronounced in the ticagrelor group. The platelet/CD34⁺ (CD61⁺/CD34⁺) conjugates were higher at baseline and reduced at follow-up while the platelet/KDR⁺ (CD61⁺/KDR⁺) conjugates were lower at baseline and increased at follow-up, both changes being more pronounced in the ticagrelor group. ADP activation of control samples significantly increased the KDR expression by CD34⁺ cells and the CD61⁺/KDR⁺ conjugates, these parameters being unaffected in patients at baseline but increased at follow-up. Short-term dual antiplatelet therapy in ACS patients restores the low platelet/KDR⁺ conjugates and CD34⁺ cell levels and improves the low membrane expression levels of KDR in these cells, an effect being more pronounced in ticagrelor-treated patients. This may represent a pleiotropic effect of antiplatelet therapy towards vascular endothelial regeneration.

Keywords:

• Acute coronary syndrome
• clopidogrel
• platelets
• progenitor cells
• ticagrelor

Acknowledgments

The authors thank the Atherothrombosis Research Center of the University of Ioannina for providing access to the laboratory equipments and facilities.

Declaration of Interest

The authors report no conflicts of interest.