Inhibition of Thrombin Receptor Signaling on α-Smooth Muscle Actin + CD34 + Progenitors Leads to Repair After Murine Immune Vascular Injury

Objective—The goal of this study was to use mice expressing human tissue factor pathway inhibitor (TFPI) on α-smooth muscle actin (α-SMA)+ cells as recipients of allogeneic aortas to gain insights into the cellular mechanisms of intimal hyperplasia (IH). Methods and Results—BALB/c aortas (H-2d) transplanted into α-TFPI–transgenic (Tg) mice (H-2b) regenerated a quiescent endothelium in contrast to progressive IH seen in C57BL/6 wild-type (WT) mice even though both developed aggressive anti-H-2d alloresponses, indicating similar vascular injuries. Adoptively transferred Tg CD34+ (but not CD34−) cells inhibited IH in WT recipients, indicating the phenotype of α-TFPI–Tg mice was due to these cells. Compared with syngeneic controls, endogenous CD34+ cells were mobilized in significant numbers after allogeneic transplantation, the majority showing sustained expression of tissue factor and protease-activated receptor-1 (PAR-1). In WT, most were CD45+ myeloid progenitors coexpressing CD31, vascular endothelial gr...