Distinct profiles of immune cell populations underlie in-stent restenosis: a cluster analysis approach

Abstract Background In-stent restenosis (ISR) is a major challenge in patients with coronary artery disease due to its association with poor clinical outcomes, quality of life and costs. ISR etiopathogenesis remains unclear, but traditional risk factors cannot fully explain ISR burden. Inflammation-driven loss of endothelial homeostasis and neoatherosclerosis are thought to hallmark ISR. Recently, a number of immune cell subsets have been related to vascular repair failure and endothelial damage, such as angiogenic T-cells (Tang), endothelial progenitor cells (EPC), senescent T-cells (CD4+CD28null), monocyte subsets and low-density granulocytes (LDG). However, these subsets have not been studied in ISR and an integrative analysis is lacking. Purpose 1) to evaluate potential alterations in vascular repair and endothelial damage cellular mediators in ISR and 2) to identify profiles associated with clinical features. Methods Case-control study including 30 patients with ≥1 previous stent implantation (15 bare metal stents (BMS) and 15 drug-eluting stents (DE)) which suffered restenosis and 30 patients with ≥1 BMS without restenosis, both confirmed in a second angiogram performed by clinical symptoms >8 months after index procedure. Cellular mediators of vascular homeostasis were quantified by flow cytometry based on their surface markers in peripheral blood (EPC: CD34+VEGFR2+CD133+; EC: CD34-VEGFR+CD133-; Tang: CD3+CD31+CXCR4+; senescent T-cells: CD4+CD28null) or in peripheral blood mononuclear cells (monocyte subsets, ACE expression; total LDG: CD15+; and LDG subsets: CD15+CD14-CD16- and CD15+CD14lowCD16+). Results Patients with ISR exhibited decreased circulating Tang (p=0.005) and EPC (p