Mobilization of progenitor cells and assessment of vessel healing after second generation drug-eluting stenting by optical coherence tomography

Masashi Sakuma; Takahisa Nasuno; Shichiro Abe; Syotaro Obi; Shigeru Toyoda; Isao Taguchi; Ryoichi Sohma; Ken-Ichi Inoue; Setsu Nishino; Koichi Node; Guiherme Attizzani; Hiram Bezerra; Marco Costa; Daniel Simon; Teruo Inoue

doi:10.1016/j.ijcha.2017.12.003

Mobilization of progenitor cells and assessment of vessel healing after second generation drug-eluting stenting by optical coherence tomography

Int J Cardiol Heart Vasc. 2018 Feb 16:18:17-24. doi: 10.1016/j.ijcha.2017.12.003. eCollection 2018 Mar.

Authors

Masashi Sakuma¹, Takahisa Nasuno¹, Shichiro Abe¹, Syotaro Obi^{1

2}, Shigeru Toyoda¹, Isao Taguchi³, Ryoichi Sohma², Ken-Ichi Inoue², Setsu Nishino^{1

4}, Koichi Node⁵, Guiherme Attizzani⁴, Hiram Bezerra⁴, Marco Costa⁴, Daniel Simon⁴, Teruo Inoue⁴

Affiliations

¹ Department of Cardiovascular Medicine, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
² Research Support Center, Dokkyo Medical University, Mibu, Tochigi, Japan.
³ Department of Cardiology, Koshigaya Hospital, Dokkkyo Medical University, Koshigaya, Japan.
⁴ Division of Cardiovascular Medicine, Harrington Heart & Vascular Institute, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
⁵ Department of Cardiovascular Medicine, Saga University, Saga, Japan.

Abstract

Background: Bone marrow-derived progenitor cells likely contribute to both endothelial- and smooth muscle cell-dependent healing responses in stent-injured vessel sites. This study aimed to assess mobilization of progenitor cells and vessel healing after zotarolimus-eluting (ZES) and everolimus-eluting (EES) stents.

Methods and results: In 63 patients undergoing coronary stent implantation, we measured circulating CD34 + CD133 + CD45low cells and serum levels of biomarkers relevant to stem cell mobilization. In 31 patients of them, we assessed vessel healing within the stented segment using optical coherence tomography (OCT) imaging. The CD34 + CD133 + CD45low cells increased 68 ± 59% 7 days after bare metal stent (BMS), 10 ± 53% after ZES (P < 0.01 vs BMS), 3 ± 49% after EES (P < 0.001 vs BMS), compared with baseline. Percent change in CD34 + CD133 + CD45low cells was positively correlated with that in stromal cell-derived factor (SDF)-1α (R = 0.29, P = 0.034). Percentage of uncovered struts was higher in the EES group (14.4 ± 17.3%), compared with the BMS (0.7 ± 1.3, P < 0.01) and ZES (0.4 ± 0.5, P < 0.01) groups. The change in CD34 + CD133 + CD45low cells showed positive correlation with OCT-quantified mean neointimal area (R = 0.48, P < 0.01). Finally, circulating mononuclear cells obtained from 5 healthy volunteers were isolated to determine the effect of sirolimus, zotarolimus and everolimus on vascular cell differentiation. The differentiation of mononuclear cells into endothelial-like cells was dose-dependently suppressed by sirolimus, zotarolimus, and everolimus.

Conclusions: Mobilization of progenitor cells was suppressed, and differentiation of mononuclear cells into endothelial-like cells was inhibited, in association with increased number of uncovered stent struts, even after second generation drug-eluting stenting. These data suggest that new approaches are necessary to enhance stent healing.

Keywords: Circulating progenitor cell; Drug-eluting stent; Optical coherence tomography; Re-endothelialization; Vascular injury.