Blood Cells, Endothelial Cells, and Circulating Extracellular Vesicles Induce Procoagulant Activity by Phosphatidylserine Exposure in Chronic Coronary Artery Disease Patients with In-stent Restenosis after Percutaneous Coronary Intervention.

Abstract

Aims: In-stent restenosis (ISR) is a significant limitation of coronary stent implantation, but the exact mechanism of ISR remains unclear. Patients after percutaneous coronary intervention (PCI) are in a hypercoagulable state; however, there is less information on its association with chronic coronary artery disease (CAD) in patients with ISR after PCI. We aimed to clarify whether or not CAD patients with ISR after PCI are in a hypercoagulable state and whether or not PS exposure on extracellular vesicles (EVs), blood cells (BCs), and endothelial cells (ECs) is involved in the hypercoagulable state.

Methods: Phosphatidylserine (PS) exposure to EVs, BCs, and ECs was analyzed using flow cytometry. Procoagulant activity (PCA) was analyzed by clotting time (CT), purified clotting complex assays, and fibrin production assays.

Results: Compared with pre-PCI or controls, levels of exposed PS on EVs, BCs, and ECs were significantly increased from 1 day, peaked at 3 months, and gradually decreased within 1 year in CAD patients after PCI, especially in CAD patients with ISR after PCI. Furthermore, their increased levels significantly decrease CT and enhance intrinsic/extrinsic FXa, thrombin, and fibrin generation. PCA was weakened by approximately 80% when lactadherin was used.

Conclusions: Our results revealed that CAD patients after PCI, especially those patients with ISR after PCI, are associated with a hypercoagulable state in which PS exposure on EVs, BCs, and ECs plays a more important role than tissue factors. Therefore, blocking PS exposure to EVs, BCs, and ECs may provide a new target for preventing ISR in these patients.