Abstract 16693: Role of PSGL-1 Expressing CD4 T Cells in Plaque Instability
Background: Adhesive interactions of leukocytes with the endothelial cells have been known to play a crucial role in atherosclerosis progression and plaque instability. In this study, we examined whether PSGL-1 expressing CD4 T cells in acute coronary syndrome (ACS) and apolipoprotein E-deficient (ApoE−/−) mice contribute to plaque instability.
Methods and Results: Fresh CD4 T cells were isolated from the peripheral blood of 36 ACS patients (AMI=23, UAP=13) and 24 healthy controls (NC). CD4 T cells from ACS strongly expressed PSGL-1 and integrin β2, but not L-selectin and integrin αM by FACS (P<0.05, P<0.05, and n.s., respectively). We investigated the thrombus-aspirating device samples (n=22) and fresh CD4 T cells derived from both the coronary artery and peripheral blood from the same ACS patients group. CD4 T cells from the coronary artery strongly expressed PSGL-1 (P<0.002), but not integrin β2 by FACS. We confirmed that culprit atherosclerotic plaques contained abundant PSGL-1 expressed CD4 T cells by immunohistochemistry. To investigate whether PSGL-1 expressing CD4 T cells from ACS have endothelial cytotoxicity, CD4 T cells were co-cultured on HUVEC monolayer. CD4 T cells from the culprit coronary artery strongly induced endothelial cell apoptosis compared to those from the peripheral blood (P<0.03) and controls (P<0.0005). CD4 T cell induced endothelial cell apoptosis correlated with the expression of PSGL-1 on CD4 T cells (R=0.788, P<0.03), and was inhibited by anti-PSGL-1 Ab (P<0.05). Furthermore, to confirm whether PSGL-1 expressed CD4 T cells were related with the progression of atherosclerosis in vivo, 9-week-old ApoE−/− mice were fed with a high-fat diet for 6 weeks with either ant-PSGL-1 Ab (100ug/mouse, n=5) or control IgG (100ug/mouse, n=5) intraperitoneal injection twice a week for 3 weeks. Oil-red-O staining and immunohistochemistry of the aortic sinus revealed that the ant-PSGL-1 Ab group suppressed the development of atherosclerotic lesions with inflammatory infiltrates and PSGL-1 expressing CD4 T cells compare with the control IgG group.
Conclusions: From these results, we demonstrated that PSGL-1 expressing CD4 T cells participate directly in the acceleration of plaque instability and incidence of ACS.
- © 2010 by American Heart Association, Inc.