Biological determinants of neointimal proliferation after intracoronary therapy with drug-eluting devices: role of endothelial progenitor cells and cytokines

Abstract

Background: We aimed to determine the influence of biological determinants of vessel remodeling, such as endothelial progenitor cells (EPC) and levels of cytokines of interleukin (IL) 1 family, after stenting with different devices. Vessel remodeling was analysed using QCA and optical coherence tomography (OCT). Methods: The study population (Octopus Trial-NCT01056744) and allocation to intervention are described in Fig. 1. EPC were counted by flow cytometry as circulating cells simultaneously expressing the CD34, CD133 and KDR epitopes. Circulating and apoptotic EPC (determined using the annexin V test), and IL1ra and IL18 levels were assessed at baseline and at f/u. Results: 6-month f/u was available in 76 pts (46 DES vs. 41 BMS+DEB). OCT analysis showed significantly more neointimal proliferation in the BMS+DEB group (15.69±7.6 mm3/cm vs 11.21±5.3 mm3/cm in DES, p=0.002). with comparable results for stent endothelialisation between both groups (uncovered stent struts: 4.1±8.9% vs. 3.8±7.3% n.s.). Interleukins correlated with age (IL1ra: r=0.46, p=0.011; IL18: r=0.4, p=0.021). In the BMS+DEB group indexed neointimal volume correlated inversely with the EPC count (r= -0.33, p=0.02) and with the proportion of noncovered struts (r= -0.59, p<0.001). Noncoverage showed a positive association with EPC (r=0.37, p=0.012) and an inverse relationship with apoptotic EPC (r= -0.33, p=0.023). ILs did not correlate with proliferation or endothelialisation. In the entire population, neointimal volume was inversely associated with the amount of EPC (r= -0.27, p=0.009) and with noncoverage (r= -0.48, p<0.001), the latter was also inversely correlated with apoptotic EPC (r= -0.29, p=0.006). Figure 1 Conclusions: Circulating and apoptotic EPC seem to influence neointimal proliferation and stent strut coverage after stenting.