P-Selectin Glycoprotein Ligand-1 (PSGL-1) Expressing CD4 T Cells Contribute Plaque Instability in Acute Coronary Syndrome

Background: Adhesion molecules have essential roles in the development of atherosclerosis. We investigated whether P-selectin glycoprotein ligand-1 (PSGL-1)-expressing CD4 T cells contribute to plaque instability in acute coronary syndrome (ACS).

Methods and results: We studied the adhesion molecules on CD4 T cells from consecutive patients with ACS treated with thrombus-aspirating device and compared them with healthy controls (n=48 each). Blood, thrombi, and plaque samples from the culprit coronary arteries were collected by thrombus aspiration performed during emergency coronary artery angiography. According to flow cytometry results, peripheral CD4 T cells from ACS patients strongly expressed PSGL-1 and Integrin β2 (P<0.05 for both) more than those from controls; culprit coronary arteries contained an abundance of PSGL-1⁺(P<0.001) but not Integrin β2⁺CD4 T cells. In addition, immunohistochemical analysis of the thrombus-aspirating device samples revealed numerous PSGL-1⁺CD4 T cells in plaques from the culprit lesions. Results from the selectin-binding assay demonstrated that activated PSGL-1⁺CD4 T cells from ACS patients bound to P- or E-Selectin after triggering the T-cell receptor, and adhered to endothelial cells under laminar flow conditions (P<0.05 and P<0.05, respectively), inducing their Apoptosis (P<0.01) via activated Caspase-3, which correlated with PSGL-1 expression (R=0.788, P=0.021) and was suppressed by application of a PSGL-1-specific antibody (P<0.05).

Conclusions: PSGL-1 contributed to cytotoxic CD4 T cell homing to the culprit coronary artery and promoted plaque instability in ACS.

Acute coronary syndrome; Atherosclerosis; Cell adhesion molecules; Lymphocytes; Plaque vulnerability.